Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Olfactory Loss and Dysfunction in Ciliopathies: Molecular Mechanisms and Potential Therapies

Author(s): Cedric R. Uytingco, Warren W. Green and Jeffrey R. Martens*

Volume 26, Issue 17, 2019

Page: [3103 - 3119] Pages: 17

DOI: 10.2174/0929867325666180105102447

Price: $65


Background: Ciliopathies are a class of inherited pleiotropic genetic disorders in which alterations in cilia assembly, maintenance, and/or function exhibit penetrance in the multiple organ systems. Olfactory dysfunction is one such clinical manifestation that has been shown in both patients and model organisms. Existing therapies for ciliopathies are limited to the treatment or management of symptoms. The last decade has seen an increase in potential curative therapeutic options including small molecules and biologics. Recent work in multiciliated olfactory sensory neurons has demonstrated the capacity of targeted gene therapy to restore ciliation in terminally differentiated cells and rescue olfactory function. This review will discuss the current understanding of the penetrance of ciliopathies in the olfactory system. Importantly, it will highlight both pharmacological and biological approaches, and their potential therapeutic value in the olfactory system and other ciliated tissues.

Methods: We undertook a structured and comprehensive search of peer-reviewed research literature encompassing in vitro, in vivo, model organism, and clinical studies. From these publications, we describe the olfactory system, and discuss the penetrance of ciliopathies and impact of cilia loss on olfactory function. In addition, we outlined the developing therapies for ciliopathies across different organ and cell culture systems, and discussed their potential therapeutic application to the mammalian olfactory system.

Results: One-hundred sixty-one manuscripts were included in the review, centering on the understanding of olfactory penetrance of ciliopathies, and discussing the potential therapeutic options for ciliopathies in the context of the mammalian olfactory system. Forty-four manuscripts were used to generate a table listing the known congenital causes of olfactory dysfunction, with the first ten listed are linked to ciliopathies. Twenty-three manuscripts were used to outline the potential of small molecules for the olfactory system. Emphasis was placed on HDAC6 inhibitors and lithium, both of which were shown to stabilize microtubule structures, contributing to ciliogenesis and cilia lengthening. Seventy-five manuscripts were used to describe gene therapy and gene therapeutic strategies. Included were the implementation of adenoviral, adeno-associated virus (AAV), and lentiviral vectors to treat ciliopathies across different organ systems and application toward the olfactory system. Thus far, adenoviral and AAVmeditated ciliary restoration demonstrated successful proof-of-principle preclinical studies. In addition, gene editing, ex vivo gene therapy, and transplantation could serve as alternative therapeutic and long-term approaches. But for all approaches, additional assessment of vector immunogenicity, specificity, and efficacy need further investigation. Currently, ciliopathy treatments are limited to symptomatic management with no curative options. However, the accessibility and amenability of the olfactory system to treatment would facilitate development and advancement of a viable therapy.

Conclusion: The findings of this review highlight the contribution of ciliopathies to a growing list of congenial olfactory dysfunctions. Promising results from other organ systems imply the feasibility of biologics, with results from gene therapies proving to be a viable therapeutic option for ciliopathies and olfactory dysfunction.

Keywords: Olfactory dysfunction, ciliopathy, olfactory epithelium, gene therapy, small molecule, olfactory loss, AAV.

Berbari, N.F.; O’Connor, A.K.; Haycraft, C.J.; Yoder, B.K. The primary cilium as a complex signaling center. Curr. Biol., 2009, 19(13), R526-R535.
[] [PMID: 19602418]
Goetz, S.C.; Anderson, K.V. The primary cilium: a signalling centre during vertebrate development. Nat. Rev. Genet., 2010, 11(5), 331-344.
[] [PMID: 20395968]
Takeda, S.; Narita, K. Structure and function of vertebrate cilia, towards a new taxonomy. Differentiation, 2012, 83(2), S4-S11.
[] [PMID: 22118931]
Ware, S.M.; Aygun, M.G. -; Hildebrandt, F. Spectrum of clinical diseases caused by disorders of primary cilia. Proc. Am. Thorac. Soc., 2011, 8(5), 444-450.
[] [PMID: 21926397]
Reiter, J.F.; Leroux, M.R. Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol., 2017, 18(9), 533-547.
[] [PMID: 28698599]
Menco, B.P.; Farbman, A.I. Genesis of cilia and microvilli of rat nasal epithelia during pre-natal development. I. Olfactory epithelium, qualitative studies. J. Cell Sci., 1985, 78, 283-310.
[PMID: 4093475]
Menco, B.P.; Farbman, A.I. Genesis of cilia and microvilli of rat nasal epithelia during pre-natal development. II. Olfactory epithelium, a morphometric analysis. J. Cell Sci., 1985, 78, 311-336.
[PMID: 4093476]
Joiner, A.M.; Green, W.W.; McIntyre, J.C.; Allen, B.L.; Schwob, J.E.; Martens, J.R. Primary cilia on horizontal basal cells regulate regeneration of the olfactory epithelium. J. Neurosci., 2015, 35(40), 13761-13772.
[] [PMID: 26446227]
Williams, C.L.; McIntyre, J.C.; Norris, S.R.; Jenkins, P.M.; Zhang, L.; Pei, Q.; Verhey, K.; Martens, J.R. Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia. Nat. Commun., 2014, 5, 5813.
[] [PMID: 25504142]
Ulloa-Aguirre, A.; Conn, P.M. Pharmacoperones as a new therapeutic approach: in vitro identification and in vivo validation of bioactive molecules. Curr. Drug Targets, 2016, 17(13), 1471-1481.
[] [PMID: 26953247]
Rutkowska, A.; Dev, K.K.; Sailer, A.W. The role of the Oxysterol/EBI2 pathway in the immune and central nervous systems. Curr. Drug Targets, 2016, 17(16), 1851-1860.
[] [PMID: 26898310]
Liapakis, G.; Matsoukas, M-T.; Karageorgos, V.; Venihaki, M.; Mavromoustakos, T.; Family, B.G. Family B G protein-coupled receptors and their ligands: from structure to function. Curr. Med. Chem., 2017, 24(31), 3323-3355.
[] [PMID: 28266266]
Hauser, A.S.; Attwood, M.M.; Rask-Andersen, M.; Schiöth, H.B.; Gloriam, D.E. Trends in GPCR drug discovery: new agents, targets and indications. Nat. Rev. Drug Discov., 2017, 16(12), 829-842.
[] [PMID: 29075003]
Temmel, A.F.P.; Quint, C.; Schickinger-Fischer, B.; Klimek, L.; Stoller, E.; Hummel, T. Characteristics of olfactory disorders in relation to major causes of olfactory loss. Arch. Otolaryngol. Head Neck Surg., 2002, 128(6), 635-641.
[] [PMID: 12049556]
Gopinath, B.; Anstey, K.J.; Sue, C.M.; Kifley, A.; Mitchell, P. Olfactory impairment in older adults is associated with depressive symptoms and poorer quality of life scores. Am. J. Geriatr. Psychiatry, 2011, 19(9), 830-834.
[] [PMID: 21422904]
Philpott, C.M.; Boak, D. The impact of olfactory disorders in the United kingdom. Chem. Senses, 2014, 39(8), 711-718.
[] [PMID: 25201900]
Holbrook, E.H.; Leopold, D.A. An updated review of clinical olfaction. Curr. Opin. Otolaryngol. Head Neck Surg., 2006, 14(1), 23-28.
[] [PMID: 16467634]
Kulaga, H.M.; Leitch, C.C.; Eichers, E.R.; Badano, J.L.; Lesemann, A.; Hoskins, B.E.; Lupski, J.R.; Beales, P.L.; Reed, R.R.; Katsanis, N. Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat. Genet., 2004, 36(9), 994-998.
[] [PMID: 15322545]
McEwen, D.P.; Koenekoop, R.K.; Khanna, H.; Jenkins, P.M.; Lopez, I.; Swaroop, A.; Martens, J.R. Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons. Proc. Natl. Acad. Sci. USA, 2007, 104(40), 15917-15922.
[[DOI: 10.1073/pnas.0704140104] [PMID: 17898177]
Tadenev, A.L.D.; Kulaga, H.M.; May-Simera, H.L.; Kelley, M.W.; Katsanis, N.; Reed, R.R. Loss of Bardet-Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting. Proc. Natl. Acad. Sci. USA, 2011, 108(25), 10320-10325.
[] [PMID: 21646512]
Mcintyre, J.C.; Davis, E.E.; Joiner, A.; Williams, C.L.; Tsai, I.; Jenkins, P.M.; Mcewen, D.P.; Zhang, L.; Escobado, J.; Thomas, S.; Szymanska, K.; Johnson, C.A.; Beales, P.L.; Green, E.D.; Mullikin, J.C.; Comparative, N.; Program, S.; Sabo, A.; Muzny, D.M.; Gibbs, R.A.; Attié-bitach, T.; Yoder, B.K.; Reed, R.R.; Katsanis, N.; Martens, J.R. Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model. Nat. Med., 2012, 18(9), 1423-1428.
Williams, C.L.; Uytingco, C.R.; Green, W.W.; McIntyre, J.C.; Ukhanov, K.; Zimmerman, A.D.; Shively, D.T.; Zhang, L.; Nishimura, D.Y.; Sheffield, V.C.; Martens, J.R. Gene therapeutic reversal of peripheral olfactory impairment in Bardet-Biedl Syndrome. Mol. Ther., 2017, 25(4), 904-916.
[] [PMID: 28237838]
Abd-El-Barr, M.M.; Sykoudis, K.; Andrabi, S.; Eichers, E.R.; Pennesi, M.E.; Tan, P.L.; Wilson, J.H.; Katsanis, N.; Lupski, J.R.; Wu, S.M. Impaired photoreceptor protein transport and synaptic transmission in a mouse model of Bardet-Biedl syndrome. Vision Res., 2007, 47(27), 3394-3407.
[] [PMID: 18022666]
Fath, M.A.; Mullins, R.F.; Searby, C.; Nishimura, D.Y.; Wei, J.; Rahmouni, K.; Davis, R.E.; Tayeh, M.K.; Andrews, M.; Yang, B.; Sigmund, C.D.; Stone, E.M.; Sheffield, V.C. Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. Hum. Mol. Genet., 2005, 14(9), 1109-1118.
[] [PMID: 15772095]
Nishimura, D.Y.; Fath, M.; Mullins, R.F.; Searby, C.; Andrews, M.; Davis, R.; Andorf, J.L.; Mykytyn, K.; Swiderski, R.E.; Yang, B.; Carmi, R.; Stone, E.M.; Sheffield, V.C. Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Proc. Natl. Acad. Sci. USA, 2004, 101(47), 16588-16593.
[] [PMID: 15539463]
Mykytyn, K.; Mullins, R.F.; Andrews, M.; Chiang, A.P.; Swiderski, R.E.; Yang, B.; Braun, T.; Casavant, T.; Stone, E.M.; Sheffield, V.C. Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proc. Natl. Acad. Sci. USA, 2004, 101(23), 8664-8669.
[] [PMID: 15173597]
Davis, R.E.; Swiderski, R.E.; Rahmouni, K.; Nishimura, D.Y.; Mullins, R.F.; Agassandian, K.; Philp, A.R.; Searby, C.C.; Andrews, M.P.; Thompson, S.; Berry, C.J.; Thedens, D.R.; Yang, B.; Weiss, R.M.; Cassell, M.D.; Stone, E.M.; Sheffield, V.C. A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Proc. Natl. Acad. Sci. USA, 2007, 104(49), 19422-19427.
[] [PMID: 18032602]
Pretorius, P.R.; Baye, L.M.; Nishimura, D.Y.; Searby, C.C.; Bugge, K.; Yang, B.; Mullins, R.F.; Stone, E.M.; Sheffield, V.C.; Slusarski, D.C. Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform. PLoS Genet., 2010, 6(3), e1000884.
[] [PMID: 20333246]
Mockel, A.; Obringer, C.; Hakvoort, T.B.M.; Seeliger, M.; Lamers, W.H.; Stoetzel, C.; Dollfus, H.; Marion, V. Pharmacological modulation of the retinal unfolded protein response in Bardet-Biedl syndrome reduces apoptosis and preserves light detection ability. J. Biol. Chem., 2012, 287(44), 37483-37494.
[] [PMID: 22869374]
Shillingford, J.M.; Murcia, N.S.; Larson, C.H.; Low, S.H.; Hedgepeth, R.; Brown, N.; Flask, C.A.; Novick, A.C.; Goldfarb, D.A.; Kramer-Zucker, A.; Walz, G.; Piontek, K.B.; Germino, G.G.; Weimbs, T. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc. Natl. Acad. Sci. USA, 2006, 103(14), 5466-5471.
[] [PMID: 16567633]
Wahl, P.R.; Serra, A.L.; Le Hir, M.; Molle, K.D.; Hall, M.N.; Wüthrich, R.P. Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol. Dial. Transplant., 2006, 21(3), 598-604.
[] [PMID: 16221708]
Masyuk, T.V.; Masyuk, A.I.; Torres, V.E.; Harris, P.C.; Larusso, N.F. Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3′,5′-cyclic monophosphate. Gastroenterology, 2007, 132(3), 1104-1116.
[] [PMID: 17383431]
Ibraghimov-Beskrovnaya, O. Molecular pathogenesis of ADPKD and development of targeted therapeutic options. Nephrol. Dial. Transplant., 2007, 22(12), 3367-3370.
[] [PMID: 17971378]
Chang, M-Y.; Ong, A.C.M. Mechanism-based therapeutics for autosomal dominant polycystic kidney disease: recent progress and future prospects. Nephron Clin. Pract., 2012, 120(1), c25-c34.
[] [PMID: 22205396]
Torres, V.E.; Chapman, A.B.; Devuyst, O.; Gansevoort, R.T.; Grantham, J.J.; Higashihara, E.; Perrone, R.D.; Krasa, H.B.; Ouyang, J.; Czerwiec, F.S. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2012, 367(25), 2407-2418.
[] [PMID: 23121377]
Skalicka, K.; Kovacs, L. Ciliotherapy-new opportunity for targeted therapy in autosomal dominant polycystic kidney disease. J. Genet. Syndr. Gene Ther., 2016, 7(5), 5-8.
Sharma, N.; Malarkey, E.B.; Berbari, N.F.; O’Connor, A.K.; Vanden Heuvel, G.B.; Mrug, M.; Yoder, B.K. Proximal tubule proliferation is insufficient to induce rapid cyst formation after cilia disruption. J. Am. Soc. Nephrol., 2013, 24(3), 456-464.
[] [PMID: 23411784]
Lee, S.H.; Somlo, S. Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease. Kidney Res. Clin. Pract., 2014, 33(2), 73-78.
[] [PMID: 26877954]
Verghese, E.; Weidenfeld, R.; Bertram, J.F.; Ricardo, S.D.; Deane, J.A. Renal cilia display length alterations following tubular injury and are present early in epithelial repair. Nephrol. Dial. Transplant., 2008, 23(3), 834-841.
[] [PMID: 17962379]
Ong, A.C.M. Primary cilia and renal cysts: does length matter? Nephrol. Dial. Transplant., 2013, 28(11), 2661-2663.
[] [PMID: 23935132]
Saito, S.; Tampe, B.; Müller, G.A.; Zeisberg, M. Primary cilia modulate balance of canonical and non-canonical Wnt signaling responses in the injured kidney. Fibrogenesis Tissue Repair, 2015, 8(1), 6.
[] [PMID: 25901180]
Yu, F.; Ran, J.; Zhou, J. Ciliopathies: does HDAC6 Represent a New Therapeutic Target? Trends Pharmacol. Sci., 2016, 37(2), 114-119.
[] [PMID: 26651415]
Plotnikova, O.V.; Nikonova, A.S.; Loskutov, Y.V.; Kozyu-lina, P.Y.; Pugacheva, E.N.; Golemis, E.A. Calmodulin activation of Aurora-A kinase (AURKA) is required during ciliary disassembly and in mitosis. Mol. Biol. Cell, 2012, 23(14), 2658-2670.
[] [PMID: 22621899]
Mergen, M.; Engel, C.; Müller, B.; Follo, M.; Schäfer, T.; Jung, M.; Walz, G. The nephronophthisis gene product NPHP2/Inversin interacts with Aurora A and interferes with HDAC6-mediated cilia disassembly. Nephrol. Dial. Transplant., 2013, 28(11), 2744-2753.
[] [PMID: 24026243]
Dere, R.; Perkins, A.L.; Bawa-Khalfe, T.; Jonasch, D.; Walker, C.L. β-catenin links von Hippel-Lindau to aurora kinase A and loss of primary cilia in renal cell carcinoma. J. Am. Soc. Nephrol., 2015, 26(3), 553-564.
[] [PMID: 25313256]
Ran, J.; Yang, Y.; Li, D.; Liu, M.; Zhou, J. Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly. Sci. Rep., 2015, 5, 12917.
[] [PMID: 26246421]
Gradilone, S.A.; Radtke, B.N.; Bogert, P.S.; Huang, B.Q.; Gajdos, G.B.; LaRusso, N.F. HDAC6 Inhibition restores ciliary expression and decreases tumor growth. Cancer Res., 2013, 73(7), 2259-LP-2270.
Kai, K.; Satoh, H.; Kajimura, T.; Kato, M.; Uchida, K.; Yamaguchi, R.; Tateyama, S.; Furuhama, K. Olfactory epithelial lesions induced by various cancer chemotherapeutic agents in mice. Toxicol. Pathol., 2004, 32(6), 701-709.
[] [PMID: 15580704]
Loktev, A.V.; Zhang, Q.; Beck, J.S.; Searby, C.C.; Scheetz, T.E.; Bazan, J.F.; Slusarski, D.C.; Sheffield, V.C.; Jackson, P.K.; Nachury, M.V. A BBSome subunit links ciliogenesis, microtubule stability, and acetylation. Dev. Cell, 2008, 15(6), 854-865.
[] [PMID: 19081074]
Nakakura, T.; Asano-Hoshino, A.; Suzuki, T.; Arisawa, K.; Tanaka, H.; Sekino, Y.; Kiuchi, Y.; Kawai, K.; Hagiwara, H. The elongation of primary cilia via the acetylation of α-tubulin by the treatment with lithium chloride in human fibroblast KD cells. Med. Mol. Morphol., 2015, 48(1), 44-53.
[] [PMID: 24760594]
Miyoshi, K.; Kasahara, K.; Miyazaki, I.; Asanuma, M. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Biochem. Biophys. Res. Commun., 2009, 388(4), 757-762.
[] [PMID: 19703416]
Thompson, C.L.; Wiles, A.; Poole, C.A.; Knight, M.M. Lithium chloride modulates chondrocyte primary cilia and inhibits Hedgehog signaling. FASEB J., 2016, 30(2), 716-726.
[] [PMID: 26499268]
Ramezani, M.; Ebrahimian, M.; Hashemi, M. Current strategies in the modification of PLGA-based gene delivery system. Curr. Med. Chem., 2017, 24(7), 728-739.
[] [PMID: 27919215]
Wang, K.; Huang, Q.; Qiu, F.; Sui, M. Non-viral delivery systems for the application in p53 cancer gene therapy. Curr. Med. Chem., 2015, 22(35), 4118-4136.
[] [PMID: 26423086]
Bhosale, R.R.; Gangadharappa, H.V.; Hani, U.; Ali, M.; Osmani, R.; Vaghela, R.; Kulkarni, P.K.; Koganti, V.S. Current perspectives on novel drug delivery systems and therapies for management of prostate cancer: an inclusive review. Curr. Drug Targets, 2017, 18(11), 1233-1249.
[] [PMID: 27296312]
Muruve, D.A. The innate immune response to adenovirus vectors. Hum. Gene Ther., 2004, 15(12), 1157-1166.
[] [PMID: 15684693]
Huang, D.; Pereboev, A.V.; Korokhov, N.; He, R.; Larocque, L.; Gravel, C.; Jaentschke, B.; Tocchi, M.; Casley, W.L.; Lemieux, M.; Curiel, D.T.; Chen, W.; Li, X. Significant alterations of biodistribution and immune responses in Balb/c mice administered with adenovirus targeted to CD40(+) cells. Gene Ther., 2008, 15(4), 298-308.
[] [PMID: 18046426]
Sammels, E.; Devogelaere, B.; Mekahli, D.; Bultynck, G.; Missiaen, L.; Parys, J.B.; Cai, Y.; Somlo, S.; De Smedt, H. Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+ release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain. J. Biol. Chem., 2010, 285(24), 18794-18805.
[] [PMID: 20375013]
Wei, F.; Karihaloo, A.; Yu, Z.; Marlier, A.; Seth, P.; Shibazaki, S.; Wang, T.; Sukhatme, V.P.; Somlo, S.; Cantley, L.G. Neutrophil gelatinase-associated lipocalin suppresses cyst growth by Pkd1 null cells in vitro and in vivo. Kidney Int., 2008, 74(10), 1310-1318.
[] [PMID: 18974761]
Park, E.Y.; Kim, B.H.; Lee, E.J.; Chang, E.; Kim, D.W.; Choi, S.Y.; Park, J.H. Targeting of receptor for advanced glycation end products suppresses cyst growth in polycystic kidney disease. J. Biol. Chem., 2014, 289(13), 9254-9262.
[] [PMID: 24515114]
Zhao, H.; Otaki, J.M.; Firestein, S. Adenovirus-mediated gene transfer in olfactory neurons in vivo. J. Neurobiol., 1996, 30(4), 521-530.
[<521:AID-NEU7>3.0.CO;2-5] [PMID: 8844515]
Holtmaat, A.J.G.D.; Hermens, W.T.J.M.C.; Oestreicher, A.B.; Gispen, W.H.; Kaplitt, M.G.; Verhaagen, J. Efficient adenoviral vector-directed expression of a foreign gene to neurons and sustentacular cells in the mouse olfactory neuroepithelium. Brain Res. Mol. Brain Res., 1996, 41(1-2), 148-156.
[] [PMID: 8883946]
Touhara, K.; Sengoku, S.; Inaki, K.; Tsuboi, A.; Hirono, J.; Sato, T.; Sakano, H.; Haga, T. Functional identification and reconstitution of an odorant receptor in single olfactory neurons. Proc. Natl. Acad. Sci. USA, 1999, 96(7), 4040-4045.
[] [PMID: 10097159]
Ivic, L.; Pyrski, M.M.; Margolis, J.W.; Richards, L.J.; Firestein, S.; Margolis, F.L. Adenoviral vector-mediated rescue of the OMP-null phenotype in vivo. Nat. Neurosci., 2000, 3(11), 1113-1120.
[] [PMID: 11036268]
Arimoto, Y.; Nagata, H.; Isegawa, N.; Kumahara, K.; Isoyama, K.; Konno, A.; Shirasawa, H. In vivo expression of adenovirus-mediated lacZ gene in murine nasal mucosa. Acta Otolaryngol., 2002, 122(6), 627-633.
[] [PMID: 12403125]
Ivic, L.; Zhang, C.; Zhang, X.; Yoon, S.O.; Firestein, S. Intracellular trafficking of a tagged and functional mammalian olfactory receptor. J. Neurobiol., 2002, 50(1), 56-68.
[] [PMID: 11748633]
Youngentob, S.L.; Pyrski, M.M.; Margolis, F.L. Adenoviral vector-mediated rescue of the OMP-null behavioral phenotype: enhancement of odorant threshold sensitivity. Behav. Neurosci., 2004, 118(3), 636-642.
[] [PMID: 15174942]
Venkatraman, G.; Behrens, M.; Pyrski, M.; Margolis, F.L. Expression of coxsackie-adenovirus receptor (CAR) in the developing mouse olfactory system. J. Neurocytol., 2005, 34(3-5), 295-305.
[] [PMID: 16841169]
Gau, P.; Rodriguez, S.; De Leonardis, C.; Chen, P.; Lin, D.M. Air-assisted intranasal instillation enhances adenoviral delivery to the olfactory epithelium and respiratory tract. Gene Ther., 2011, 18(5), 432-436.
[] [PMID: 21085195]
Lemiale, F.; Kong, W.P.; Akyürek, L.M.; Ling, X.; Huang, Y.; Chakrabarti, B.K.; Eckhaus, M.; Nabel, G.J. Enhanced mucosal immunoglobulin A response of intranasal adenoviral vector human immunodeficiency virus vaccine and localization in the central nervous system. J. Virol., 2003, 77(18), 10078-10087.
[] [PMID: 12941918]
Damjanovic, D.; Zhang, X.; Mu, J.; Fe Medina, M.; Xing, Z. Organ distribution of transgene expression following intranasal mucosal delivery of recombinant replication-defective adenovirus gene transfer vector. Genet. Vaccines Ther., 2008, 6, 5.
[] [PMID: 18261231]
Doi, K.; Nibu, K.; Ishida, H.; Okado, H.; Terashima, T. Adenovirus-mediated gene transfer in olfactory epithelium and olfactory bulb: a long-term study. Ann. Otol. Rhinol. Laryngol., 2005, 114(8), 629-633.
[] [PMID: 16190096]
Zincarelli, C.; Soltys, S.; Rengo, G.; Rabinowitz, J.E. Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol. Ther., 2008, 16(6), 1073-1080.
[] [PMID: 18414476]
Samulski, R.J.; Zhu, X.; Xiao, X.; Brook, J.D.; Housman, D.E.; Epstein, N.; Hunter, L.A. Targeted integration of adeno-associated virus (AAV) into human chromosome 19. EMBO J., 1991, 10(12), 3941-3950.
[] [PMID: 1657596]
Narfström, K.; Katz, M.L.; Ford, M.; Redmond, T.M.; Rakoczy, E.; Bragadóttir, R. In vivo gene therapy in young and adult RPE65-/- dogs produces long-term visual improvement. J. Hered., 2003, 94(1), 31-37.
[] [PMID: 12692160]
Narfström, K.; Katz, M.L.; Bragadottir, R.; Seeliger, M.; Boulanger, A.; Redmond, T.M.; Caro, L.; Lai, C.M.; Rakoczy, P.E. Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Invest. Ophthalmol. Vis. Sci., 2003, 44(4), 1663-1672.
[] [PMID: 12657607]
Le Meur, G.; Stieger, K.; Smith, A.J.; Weber, M.; Deschamps, J.Y.; Nivard, D.; Mendes-Madeira, A.; Provost, N.; Péréon, Y.; Cherel, Y.; Ali, R.R.; Hamel, C.; Moullier, P.; Rolling, F. Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium. Gene Ther., 2007, 14(4), 292-303.
[] [PMID: 17024105]
Acland, G.M.; Aguirre, G.D.; Bennett, J.; Aleman, T.S.; Cideciyan, A.V.; Bennicelli, J.; Dejneka, N.S.; Pearce-Kelling, S.E.; Maguire, A.M.; Palczewski, K.; Hauswirth, W.W.; Jacobson, S.G. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol. Ther., 2005, 12(6), 1072-1082.
[] [PMID: 16226919]
Bainbridge, J.W.B.; Smith, A.J.; Barker, S.S.; Robbie, S.; Henderson, R.; Balaggan, K.; Viswanathan, A.; Holder, G.E.; Stockman, A.; Tyler, N.; Petersen-Jones, S.; Bhattacharya, S.S.; Thrasher, A.J.; Fitzke, F.W.; Carter, B.J.; Rubin, G.S.; Moore, A.T.; Ali, R.R. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N. Engl. J. Med., 2008, 358(21), 2231-2239.
[] [PMID: 18441371]
Cideciyan, A.V.; Jacobson, S.G.; Beltran, W.A.; Sumaroka, A.; Swider, M.; Iwabe, S.; Roman, A.J.; Olivares, M.B.; Schwartz, S.B.; Komáromy, A.M.; Hauswirth, W.W.; Aguirre, G.D. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc. Natl. Acad. Sci. USA, 2013, 110(6), E517-E525.
[] [PMID: 23341635]
Bainbridge, J.W.B.; Mehat, M.S.; Sundaram, V.; Robbie, S.J.; Barker, S.E.; Ripamonti, C.; Georgiadis, A.; Mowat, F.M.; Beattie, S.G.; Gardner, P.J.; Feathers, K.L.; Luong, V.A.; Yzer, S.; Balaggan, K.; Viswanathan, A.; de Ravel, T.J.L.; Casteels, I.; Holder, G.E.; Tyler, N.; Fitzke, F.W.; Weleber, R.G.; Nardini, M.; Moore, A.T.; Thompson, D.A.; Petersen-Jones, S.M.; Michaelides, M.; van den Born, L.I.; Stockman, A.; Smith, A.J.; Rubin, G.; Ali, R.R. Long-term effect of gene therapy on Leber’s congenital amaurosis. N. Engl. J. Med., 2015, 372(20), 1887-1897.
[] [PMID: 25938638]
Simons, D.L.; Boye, S.L.; Hauswirth, W.W.; Wu, S.M. Gene therapy prevents photoreceptor death and preserves retinal function in a Bardet-Biedl syndrome mouse model. Proc. Natl. Acad. Sci. USA, 2011, 108(15), 6276-6281.
[] [PMID: 21444805]
Seo, S.; Mullins, R.F.; Dumitrescu, A.V.; Bhattarai, S.; Gratie, D.; Wang, K.; Stone, E.M.; Sheffield, V.; Drack, A.V. Subretinal gene therapy of mice with Bardet-Biedl syndrome type 1. Invest. Ophthalmol. Vis. Sci., 2013, 54(9), 6118-6132.
[] [PMID: 23900607]
Limberis, M.P.; Wilson, J.M. Adeno-associated virus serotype 9 vectors transduce murine alveolar and nasal epithelia and can be readministered. Proc. Natl. Acad. Sci. USA, 2006, 103(35), 12993-12998.
[] [PMID: 16938846]
Limberis, M.P.; Vandenberghe, L.H.; Zhang, L.; Pickles, R.J.; Wilson, J.M. Transduction efficiencies of novel AAV vectors in mouse airway epithelium in vivo and human ciliated airway epithelium in vitro. Mol. Ther., 2009, 17(2), 294-301.
[] [PMID: 19066597]
Cao, L.; Schrank, B.R.; Rodriguez, S.; Benz, E.G.; Moulia, T.W.; Rickenbacher, G.T.; Gomez, A.C.; Levites, Y.; Edwards, S.R.; Golde, T.E.; Hyman, B.T.; Barnea, G.; Albers, M.W. Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo. Nat. Commun., 2012, 3, 1009.
[] [PMID: 22910355]
Burnight, E.R.; Wiley, L.A.; Drack, A.V.; Braun, T.A.; Anfinson, K.R.; Kaalberg, E.E.; Halder, J.A.; Affatigato, L.M.; Mullins, R.F.; Stone, E.M.; Tucker, B.A. CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype. Gene Ther., 2014, 21(7), 662-672.
[] [PMID: 24807808]
Ostrowski, L.E.; Yin, W.; Patel, M.; Sechelski, J.; Rogers, T.; Burns, K.; Grubb, B.R.; Olsen, J.C. Restoring ciliary function to differentiated primary ciliary dyskinesia cells with a lentiviral vector. Gene Ther., 2014, 21(3), 253-261.
[] [PMID: 24451115]
Chhin, B.; Negre, D.; Merrot, O.; Pham, J.; Tourneur, Y.; Ressnikoff, D.; Jaspers, M.; Jorissen, M.; Cosset, F.L.; Bouvagnet, P. Ciliary beating recovery in deficient human airway epithelial cells after lentivirus ex vivo gene therapy. PLoS Genet., 2009, 5(3), e1000422.
[] [PMID: 19300481]
Sinn, P.L.; Burnight, E.R.; Hickey, M.A.; Blissard, G.W.; McCray, P.B., Jr Persistent gene expression in mouse nasal epithelia following feline immunodeficiency virus-based vector gene transfer. J. Virol., 2005, 79(20), 12818-12827.
[] [PMID: 16188984]
Chen, H.; Dadsetan, S.; Fomina, A.F.; Gong, Q. Expressing exogenous functional odorant receptors in cultured olfactory sensory neurons. Neural Dev., 2008, 3(1), 22.
[] [PMID: 18786248]
Sadrian, B.; Chen, H.; Gong, Q. Lentivirus-mediated genetic manipulation and visualization of olfactory sensory neurons in vivo. J. Vis. Exp., 2011, 51, 5-8.
[PMID: 21633336]
Sinn, P.L.; Arias, A.C.; Brogden, K.A.; McCray, P.B., Jr Lentivirus vector can be readministered to nasal epithelia without blocking immune responses. J. Virol., 2008, 82(21), 10684-10692.
[] [PMID: 18768988]
Ranzani, M.; Cesana, D.; Bartholomae, C.C.; Sanvito, F.; Pala, M.; Benedicenti, F.; Gallina, P.; Sergi, L.S.; Merella, S.; Bulfone, A.; Doglioni, C.; von Kalle, C.; Kim, Y.J.; Schmidt, M.; Tonon, G.; Naldini, L.; Montini, E. Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer. Nat. Methods, 2013, 10(2), 155-161.
[] [PMID: 23314173]
Papayannakos, C.; Daniel, R. Understanding lentiviral vector chromatin targeting: working to reduce insertional mutagenic potential for gene therapy. Gene Ther., 2013, 20(6), 581-588.
[] [PMID: 23171920]
Chakraborty, C.; Teoh, S.L.; Das, S. The smart programmable CRISPR technology: A next generation genome editing tool for investigators. Curr. Drug Targets, 2017, 18(14), 1653-1663.
[] [PMID: 27231109]
LaFountaine, J.S.; Fathe, K.; Smyth, H.D.C. Delivery and therapeutic applications of gene editing technologies ZFNs, TALENs, and CRISPR/Cas9. Int. J. Pharm., 2015, 494(1), 180-194.
[] [PMID: 26278489]
Lee, C.M.; Flynn, R.; Hollywood, J.A.; Scallan, M.F.; Harrison, P.T. Correction of the ΔF508 mutation in the cystic fibrosis transmembrane conductance regulator gene by zinc-finger nuclease homology-directed repair. Biores. Open Access, 2012, 1(3), 99-108.
Crane, A.M.; Kramer, P.; Bui, J.H.; Chung, W.J.; Li, X.S.; Gonzalez-Garay, M.L.; Hawkins, F.; Liao, W.; Mora, D.; Choi, S.; Wang, J.; Sun, H.C.; Paschon, D.E.; Guschin, D.Y.; Gregory, P.D.; Kotton, D.N.; Holmes, M.C.; Sorscher, E.J.; Davis, B.R. Targeted correction and restored function of the CFTR gene in cystic fibrosis induced pluripotent stem cells. Stem Cell Reports, 2015, 4(4), 569-577.
[] [PMID: 25772471]
Lai, M.; Pifferi, M.; Bush, A.; Piras, M.; Michelucci, A.; Di Cicco, M.; del Grosso, A.; Quaranta, P.; Cursi, C.; Tantillo, E.; Franceschi, S.; Mazzanti, M.C.; Simi, P.; Saggese, G.; Boner, A.; Pistello, M. Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia. J. Med. Genet., 2016, 53(4), 242-249.
[] [PMID: 26729821]
Ruan, G.X.; Barry, E.; Yu, D.; Lukason, M.; Cheng, S.H.; Scaria, A. CRISPR/Cas9-mediated genome editing as a therapeutic approach for leber congenital amaurosis 10. Mol. Ther., 2017, 25(2), 331-341.
[] [PMID: 28109959]
Li, Y.; Zhang, J.; Chen, D.; Yang, P.; Jiang, F.; Wang, X.; Kang, L. CRISPR/Cas9 in locusts: Successful establishment of an olfactory deficiency line by targeting the mutagenesis of an odorant receptor co-receptor (Orco). Insect Biochem. Mol. Biol., 2016, 79, 27-35.
[] [PMID: 27744049]
Koutroumpa, F.A.; Monsempes, C.; François, M-C.; de Cian, A.; Royer, C.; Concordet, J-P.; Jacquin-Joly, E. Heritable genome editing with CRISPR/Cas9 induces anosmia in a crop pest moth. Sci. Rep., 2016, 6(1), 29620.
[] [PMID: 27403935]
Trible, W.; Olivos-Cisneros, L.; McKenzie, S.K.; Saragosti, J.; Chang, N-C.; Matthews, B.J.; Oxley, P.R.; Kronauer, D.J.C. Orco mutagenesis causes loss of antennal lobe glomeruli and impaired social behavior in ants. Cell, 2017, 170(4), 727-735.e10.
[] [PMID: 28802042]
Yan, H.; Opachaloemphan, C.; Mancini, G.; Yang, H.; Gallitto, M.; Mlejnek, J.; Leibholz, A.; Haight, K.; Ghaninia, M.; Huo, L.; Perry, M.; Slone, J.; Zhou, X.; Traficante, M.; Penick, C.A.; Dolezal, K.; Gokhale, K.; Stevens, K.; Fetter-Pruneda, I.; Bonasio, R.; Zwiebel, L.J.; Berger, S.L.; Liebig, J.; Reinberg, D.; Desplan, C. An engineered orco mutation produces aberrant social behavior and defective neural development in ants. Cell, 2017, 170(4), 736-747.e9.
[] [PMID: 28802043]
Farbman, A.I. Olfactory neurogenesis: genetic or environmental controls? Trends Neurosci., 1990, 13(9), 362-365.
[] [PMID: 1699323]
Mackay-Sim, A.; Kittel, P.W. On the life span of olfactory receptor neurons. Eur. J. Neurosci., 1991, 3(3), 209-215.
[] [PMID: 12106197]
Goldstein, B.J.; Fang, H.; Youngentob, S.L.; Schwob, J.E. Transplantation of multipotent progenitors from the adult olfactory epithelium. Neuroreport, 1998, 9(7), 1611-1617.
[] [PMID: 9631475]
Chen, X.; Fang, H.; Schwob, J.E. Multipotency of purified, transplanted globose basal cells in olfactory epithelium. J. Comp. Neurol., 2004, 469(4), 457-474.
[] [PMID: 14755529]
Schnittke, N.; Herrick, D.B.; Lin, B.; Peterson, J.; Coleman, J.H.; Packard, A.I.; Jang, W.; Schwob, J.E. Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium. Proc. Natl. Acad. Sci. USA, 2015, 112(36), E5068-E5077.
[] [PMID: 26305958]
Hummel, T.; Rissom, K.; Reden, J.; Hähner, A.; Weidenbecher, M.; Hüttenbrink, K-B. Effects of olfactory training in patients with olfactory loss. Laryngoscope, 2009, 119(3), 496-499.
[] [PMID: 19235739]
Jiang, R.S.; Twu, C.W.; Liang, K.L. The effect of olfactory training on the odor threshold in patients with traumatic anosmia. Am. J. Rhinol. Allergy, 2017, 31(5), 317-322.
[] [PMID: 28859708]
Damm, M.; Pikart, L.K.; Reimann, H.; Burkert, S.; Göktas, Ö.; Haxel, B.; Frey, S.; Charalampakis, I.; Beule, A.; Renner, B.; Hummel, T.; Hüttenbrink, K.B. Olfactory training is helpful in postinfectious olfactory loss: a randomized, controlled, multicenter study. Laryngoscope, 2014, 124(4), 826-831.
[] [PMID: 23929687]
Konstantinidis, I.; Tsakiropoulou, E.; Constantinidis, J. Long term effects of olfactory training in patients with post-infectious olfactory loss. Rhinology, 2016, 54(2), 170-175.
[] [PMID: 27017331]
Kollndorfer, K.; Kowalczyk, K.; Hoche, E.; Mueller, C.A.; Pollak, M.; Trattnig, S.; Schöpf, V. Recovery of olfactory function induces neuroplasticity effects in patients with smell loss. Neural Plast., 2014, 2014, 140419.
[] [PMID: 25544900]
Hida, K.; Lai, S.K.; Suk, J.S.; Won, S.Y.; Boyle, M.P.; Hanes, J. Common gene therapy viral vectors do not efficiently penetrate sputum from cystic fibrosis patients. PLoS One, 2011, 6(5), e19919.
[] [PMID: 21637751]
Kitson, C.; Angel, B.; Judd, D.; Rothery, S.; Severs, N.J. Dewar, a; Huang, L.; Wadsworth, S. C.; Cheng, S. H.; Geddes, D. M.; Alton, E. W. The extra- and intracellular barriers to lipid and adenovirus-mediated pulmonary gene transfer in native sheep airway epithelium. Gene Ther., 1999, 6(4), 534-546.
[] [PMID: 10476213]
Knowles, M.R.; Hohneker, K.W.; Zhou, Z.; Olsen, J.C.; Noah, T.L.; Hu, P.C.; Leigh, M.W.; Engelhardt, J.F.; Edwards, L.J.; Jones, K.R. A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N. Engl. J. Med., 1995, 333(13), 823-831.
[] [PMID: 7544439]
Novarino, G.; Akizu, N.; Gleeson, J.G. Modeling human disease in humans: the ciliopathies. Cell, 2011, 147(1), 70-79.
[] [PMID: 21962508]
Katsanis, N. Triallelic inheritance in Bardet-Biedl syndrome, a mendelian recessive Disorder. Science, 2001, 293(5538), 2256-2259.
Katsanis, N.; Eichers, E.R.; Ansley, S.J.; Lewis, R.A.; Kayserili, H.; Hoskins, B.E.; Scambler, P.J.; Beales, P.L.; Lupski, J.R. BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance. Am. J. Hum. Genet., 2002, 71(1), 22-29.
[] [PMID: 12016587]
Joseph, P.M.; O’Sullivan, B.P.; Lapey, A.; Dorkin, H.; Oren, J.; Balfour, R.; Perricone, M.A.; Rosenberg, M.; Wadsworth, S.C.; Smith, A.E.; St George, J.A.; Meeker, D.P. Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. I. Methods, safety, and clinical implications. Hum. Gene Ther., 2001, 12(11), 1369-1382.
[] [PMID: 11485629]
Mingozzi, F.; High, K.A. Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood, 2013, 122(1), 23-36.
[] [PMID: 23596044]
Braun, J.J.; Noblet, V.; Durand, M.; Scheidecker, S.; Zinetti-Bertschy, A.; Foucher, J.; Marion, V.; Muller, J.; Riehm, S.; Dollfus, H.; Kremer, S. Olfaction evaluation and correlation with brain atrophy in Bardet-Biedl syndrome. Clin. Genet., 2014, 86(6), 521-529.
[] [PMID: 24684473]
Iannaccone, A.; Mykytyn, K.; Persico, A. M.; Searby, C. C.; Baldi, A.; Jablonski, M. M.; Sheffield, V. C. Clinical evidence of decreased olfaction in bardet-biedl syndrome caused by a deletion in the BBS4 gene. Am. J. Med. Genet., 2005, 132 A(4), 343-346.
Coppieters, F.; Lefever, S.; Leroy, B.P.; De Baere, E. CEP290, a gene with many faces: mutation overview and presentation of CEP290base. Hum. Mutat., 2010, 31(10), 1097-1108.
[] [PMID: 20690115]
Ahdab-Barmada, M.; Claassen, D. A distinctive triad of malformations of the central nervous system in the Meckel-Gruber syndrome. J. Neuropathol. Exp. Neurol., 1990, 49(6), 610-620.
[] [PMID: 2230839]
Pluznick, J.L.; Rodriguez-Gil, D.J.; Hull, M.; Mistry, K.; Gattone, V.; Johnson, C.A.; Weatherbee, S.; Greer, C.A.; Caplan, M.J. Renal cystic disease proteins play critical roles in the organization of the olfactory epithelium. PLoS One, 2011, 6(5), e19694.
[] [PMID: 21614130]
Chang, B.; Khanna, H.; Hawes, N.; Jimeno, D.; He, S.; Lillo, C.; Parapuram, S.K.; Cheng, H.; Scott, A.; Hurd, R.E.; Sayer, J.A.; Otto, E.A.; Attanasio, M.; O’Toole, J.F.; Jin, G.; Shou, C.; Hildebrandt, F.; Williams, D.S.; Heckenlively, J.R.; Swaroop, A. In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum. Mol. Genet., 2006, 15(11), 1847-1857.
[] [PMID: 16632484]
Caspary, T.; Larkins, C.E.; Anderson, K.V. The graded response to Sonic Hedgehog depends on cilia architecture. Dev. Cell, 2007, 12(5), 767-778.
[] [PMID: 17488627]
Sun, Z.; Amsterdam, A.; Pazour, G.J.; Cole, D.G.; Miller, M.S.; Hopkins, N. A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney. Development, 2004, 131(16), 4085-4093.
[] [PMID: 15269167]
Gibberd, F.B.; Feher, M.D.; Sidey, M.C. Wierzbicki, a S. Smell testing: an additional tool for identification of adult refsum’s disease. J. Neurol. Neurosurg. Psychiatry, 2005, 2004(75), 1334-1336.
Wierzbicki, A.S.; Lloyd, M.D.; Schofield, C.J.; Feher, M.D.; Gibberd, F.B. Refsum’s disease: a peroxisomal disorder affecting phytanic acid α-oxidation. J. Neurochem., 2002, 80(5), 727-735.
[] [PMID: 11948235]
Abdel-Hak, B.; Gunkel, A.; Kanonier, G.; Schrott-Fischer, A.; Ulmer, H.; Thumfart, W. Ciliary beat frequency, olfaction and endoscopic sinus surgery. ORL J. Otorhinolaryngol. Relat. Spec., 1998, 60(4), 202-205.
[] [PMID: 9646307]
Papon, J.F.; Perrault, I.; Coste, A.; Louis, B.; Gérard, X.; Hanein, S.; Fares-Taie, L.; Gerber, S.; Defoort-Dhelle-mmes, S.; Vojtek, A.M.; Kaplan, J.; Rozet, J.M.; Escudier, E. Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations. J. Med. Genet., 2010, 47(12), 829-834.
[] [PMID: 20805370]
Lehman, A.M.; Eydoux, P.; Doherty, D.; Glass, I.A.; Chitayat, D.; Chung, B.Y.H.; Langlois, S.; Yong, S.L.; Lowry, R.B.; Hildebrandt, F.; Trnka, P. Co-occurrence of Joubert syndrome and Jeune asphyxiating thoracic dystrophy. Am. J. Med. Genet. A., 2010, 152A(6), 1411-1419.
[PMID: 20503315]
Maione, L.; Cantone, E.; Nettore, I.C.; Cerbone, G.; De Brasi, D.; Maione, N.; Young, J.; Di Somma, C.; Sinisi, A.A.; Iengo, M.; Macchia, P.E.; Pivonello, R.; Colao, A. Flavor perception test: evaluation in patients with Kallmann syndrome. Endocrine, 2016, 52(2), 236-243.
[] [PMID: 26209039]
Koenigkam-Santos, M.; Santos, A.C.; Versiani, B.R.; Diniz, P.R.B.; Junior, J.E.; de Castro, M. Quantitative magnetic resonance imaging evaluation of the olfactory system in Kallmann syndrome: correlation with a clinical smell test. Neuroendocrinology, 2011, 94(3), 209-217.
[] [PMID: 21606642]
Dodé, C.; Rondard, P. PROK2/PROKR2 Signaling and Kallmann Syndrome. Front. Endocrinol. (Lausanne), 2013, 4, 19.
[] [PMID: 23596439]
Mitchell, A.L.; Dwyer, A.; Pitteloud, N.; Quinton, R. Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory. Trends Endocrinol. Metab., 2011, 22(7), 249-258.
[PMID: 21511493]
Bojesen, A.; Juul, S.; Gravholt, C.H. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J. Clin. Endocrinol. Metab., 2003, 88(2), 622-626.
[] [PMID: 12574191]
Lewkowitz-Shpuntoff, H.M.; Hughes, V.A.; Plummer, L.; Au, M.G.; Doty, R.L.; Seminara, S.B.; Chan, Y.M.; Pitteloud, N.; Crowley, W.F., Jr; Balasubramanian, R. Olfactory phenotypic spectrum in idiopathic hypogonadotropic hypogonadism: pathophysiological and genetic implications. J. Clin. Endocrinol. Metab., 2012, 97(1), E136-E144.
[] [PMID: 22072740]
Vuorela, P.E.; Penttinen, M.T.; Hietala, M.H.; Laine, J.O.; Huoponen, K.A.; Kääriäinen, H.A. A familial CHARGE syndrome with a CHD7 nonsense mutation and new clinical features. Clin. Dysmorphol., 2008, 17(4), 249-253.
[] [PMID: 18978652]
Jongmans, M.C.J.; van Ravenswaaij-Arts, C.M.A.; Pitteloud, N.; Ogata, T.; Sato, N.; Claahsen-van der Grinten, H.L.; van der Donk, K.; Seminara, S.; Bergman, J.E.H.; Brunner, H.G.; Crowley, W.F., Jr; Hoefsloot, L.H. CHD7 mutations in patients initially diagnosed with Kallmann syndrome--the clinical overlap with CHARGE syndrome. Clin. Genet., 2009, 75(1), 65-71.
[] [PMID: 19021638]
Jansen, F.; Kalbe, B.; Scholz, P.; Mikosz, M.; Wunderlich, K.A.; Kurtenbach, S.; Nagel-Wolfrum, K.; Wolfrum, U.; Hatt, H.; Osterloh, S. Impact of the Usher syndrome on olfaction. Hum. Mol. Genet., 2016, 25(3), 524-533.
[] [PMID: 26620972]
Seeliger, M.; Pfister, M.; Gendo, K.; Paasch, S.; Apfelstedt-Sylla, E.; Plinkert, P.; Zenner, H-P.; Zrenner, E. Comparative study of visual, auditory, and olfactory function in Usher syndrome. Graefes Arch. Clin. Exp. Ophthalmol., 1999, 237(4), 301-307.
[] [PMID: 10208263]
Ribeiro, J.C.; Oliveiros, B.; Pereira, P.; António, N.; Hummel, T.; Paiva, A.; Silva, E.D. Accelerated age-related olfactory decline among type 1 Usher patients. Sci. Rep., 2016, 6(1), 28309.
[] [PMID: 27329700]
Marietta, J.; Walters, K.S.; Burgess, R.; Ni, L.; Fukushima, K.; Moore, K.C.; Hejtmancik, J.F.; Smith, R.J.H. Usher’s syndrome type IC: clinical studies and fine-mapping the disease locus. Ann. Otol. Rhinol. Laryngol., 1997, 106(2), 123-128.
[] [PMID: 9041816]
Reiners, J.; Nagel-Wolfrum, K.; Jürgens, K.; Märker, T.; Wolfrum, U. Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease. Exp. Eye Res., 2006, 83(1), 97-119.
[] [PMID: 16545802]
Endoh-Yamagami, S.; Karkar, K.M.; May, S.R.; Cobos, I.; Thwin, M.T.; Long, J.E.; Ashique, A.M.; Zarbalis, K.; Rubenstein, J.L.R.; Peterson, A.S. A mutation in the pericentrin gene causes abnormal interneuron migration to the olfactory bulb in mice. Dev. Biol., 2010, 340(1), 41-53.
[] [PMID: 20096683]
Hori, A.; Tamagawa, K.; Eber, S.W.; Westmeier, M.; Hansmann, I. Neuropathology of Seckel syndrome in fetal stage with evidence of intrauterine developmental retardation. Acta Neuropathol., 1987, 74(4), 397-401.
[] [PMID: 3687392]
Brasseur, B.; Martin, C. M.; Cayci, Z.; Burmeister, L.; Schimmenti, L. A. Bosma arhinia microphthalmia syndrome: Clinical report and review of the literature. Am. J. Med. Genet. Part A ., 2016, 170(5)
Graham, J. M.; Lee, J. Bosma arhinia microphthalmia syndrome. Am. J. Med. Genet., 2006, 140 A(2), 189-193.
Lahiry, P.; Wang, J.; Robinson, J.F.; Turowec, J.P.; Litchfield, D.W.; Lanktree, M.B.; Gloor, G.B.; Puffenberger, E.G.; Strauss, K.A.; Martens, M.B.; Ramsay, D.A.; Rupar, C.A.; Siu, V.; Hegele, R.A. A multiplex human syndrome implicates a key role for intestinal cell kinase in development of central nervous, skeletal, and endocrine systems. Am. J. Hum. Genet., 2009, 84(2), 134-147.
[] [PMID: 19185282]
Moerman, P.; Fryns, J.P. Oral-facial-digital syndrome type IV (Mohr-Majewski syndrome): a fetopathological study. Genet. Couns., 1998, 9(1), 39-43.
[PMID: 9555586]
Thomas, S.; Legendre, M.; Saunier, S.; Bessières, B.; Alby, C.; Bonnière, M.; Toutain, A.; Loeuillet, L.; Szymanska, K.; Jossic, F.; Gaillard, D.; Yacoubi, M.T.; Mougou-Zerelli, S.; David, A.; Barthez, M.A.; Ville, Y.; Bole-Feysot, C.; Nitschke, P.; Lyonnet, S.; Munnich, A.; Johnson, C.A.; Encha-Razavi, F.; Cormier-Daire, V.; Thauvin-Robinet, C.; Vekemans, M.; Attié-Bitach, T. TCTN3 mutations cause Mohr-Majewski syndrome. Am. J. Hum. Genet., 2012, 91(2), 372-378.
[] [PMID: 22883145]
Spranger, J.; Grimm, B.; Weller, M.; Weissenbacher, G.; Herrmann, J.; Gilbert, E.; Krepler, R. Short rib-polydactyly (SRP) syndromes, types Majewski and Saldino-Noonan. Z. Kinderheilkd., 1974, 116(2), 73-94.
[] [PMID: 4816160]
Sailani, M.R.; Jingga, I. MirMazlomi, S.H.; Bitarafan, F.; Bernstein, J.A.; Snyder, M.P.; Garshasbi, M. Isolated congenital anosmia and CNGA2 mutation. Sci. Rep., 2017, 7(1), 2667.
[] [PMID: 28572688]
Karstensen, H.G.; Mang, Y.; Fark, T.; Hummel, T.; Tommerup, N. The first mutation in CNGA2 in two brothers with anosmia. Clin. Genet., 2015, 88(3), 293-296.
[] [PMID: 25156905]
Alkelai, A.; Olender, T.; Haffner-Krausz, R.; Tsoory, M.M.; Boyko, V.; Tatarskyy, P.; Gross-Isseroff, R.; Milgrom, R.; Shushan, S.; Blau, I.; Cohn, E.; Beeri, R.; Levy-Lahad, E.; Pras, E.; Lancet, D. A role for TENM1 mutations in congenital general anosmia. Clin. Genet., 2016, 90(3), 211-219.
[] [PMID: 27040985]
Weiss, J.; Pyrski, M.; Jacobi, E.; Bufe, B.; Willnecker, V.; Schick, B.; Zizzari, P.; Gossage, S.J.; Greer, C.A.; Leinders-Zufall, T.; Woods, C.G.; Wood, J.N.; Zufall, F. Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature, 2011, 472(7342), 186-190.
[] [PMID: 21441906]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy