Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment
dc.contributor.author | Rendtorff, Nanna D. | en_US |
dc.contributor.author | Lodahl, Marianne | en_US |
dc.contributor.author | Boulahbel, Houda | en_US |
dc.contributor.author | Johansen, Ida R. | en_US |
dc.contributor.author | Pandya, Arti | en_US |
dc.contributor.author | Welch, Katherine O. | en_US |
dc.contributor.author | Norris, Virginia W. | en_US |
dc.contributor.author | Arnos, Kathleen S. | en_US |
dc.contributor.author | Bitner-Glindzicz, Maria | en_US |
dc.contributor.author | Emery, Sarah B. | en_US |
dc.contributor.author | Mets, Marilyn B. | en_US |
dc.contributor.author | Fagerheim, Toril | en_US |
dc.contributor.author | Eriksson, Kristina | en_US |
dc.contributor.author | Hansen, Lars | en_US |
dc.contributor.author | Bruhn, Helene | en_US |
dc.contributor.author | Möller, Claes | en_US |
dc.contributor.author | Lindholm, Sture | en_US |
dc.contributor.author | Ensgaard, Stefan | en_US |
dc.contributor.author | Lesperance, Marci M. | en_US |
dc.contributor.author | Tranebjaerg, Lisbeth | en_US |
dc.date.accessioned | 2011-06-10T14:20:53Z | |
dc.date.available | 2012-07-12T17:42:23Z | en_US |
dc.date.issued | 2011-06 | en_US |
dc.identifier.citation | Rendtorff, Nanna D.; Lodahl, Marianne; Boulahbel, Houda; Johansen, Ida R.; Pandya, Arti; Welch, Katherine O.; Norris, Virginia W.; Arnos, Kathleen S.; Bitner-Glindzicz, Maria; Emery, Sarah B.; Mets, Marilyn B.; Fagerheim, Toril; Eriksson, Kristina; Hansen, Lars; Bruhn, Helene; Möller, Claes; Lindholm, Sture; Ensgaard, Stefan; Lesperance, Marci M.; Tranebjaerg, Lisbeth (2011). "Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment." American Journal of Medical Genetics Part A 155(6): 1298-1313. <http://hdl.handle.net/2027.42/84383> | en_US |
dc.identifier.issn | 1552-4825 | en_US |
dc.identifier.issn | 1552-4833 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/84383 | |
dc.description.abstract | Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1 . In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and almost exclusively attributed to mutations in the Optic Atrophy-1 gene ( OPA1 ), most commonly the p.R445H mutation. We present eight probands and their families from the US, Sweden, and UK with OA and SNHL, whom we analyzed for mutations in OPA1 and WFS1 . Among these families, we found three heterozygous missense mutations in WFS1 segregating with OA and SNHL: p.A684V (six families), and two novel mutations, p.G780S and p.D797Y, all involving evolutionarily conserved amino acids and absent from 298 control chromosomes. Importantly, none of these families harbored the OPA1 p.R445H mutation. No mitochondrial DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild-type wolframin, strongly indicating that the mutation is disease-causing. Our data support OA and SNHL as a phenotype caused by dominant mutations in WFS1 in these additional eight families. Importantly, our data provide the first evidence that a single, recurrent mutation in WFS1 , p.A684V, may be a common cause of ADOA and SNHL, similar to the role played by the p.R445H mutation in OPA1 . Our findings suggest that patients who are heterozygous for WFS1 missense mutations should be carefully clinically examined for OA and other manifestations of Wolfram syndrome. © 2011 Wiley-Liss, Inc. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Genetics | en_US |
dc.title | Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Division of Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Division of Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine (ICMM), The Panum Institute, University of Copenhagen, Copenhagen, Denmark | en_US |
dc.contributor.affiliationother | Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine (ICMM), The Panum Institute, University of Copenhagen, Copenhagen, Denmark | en_US |
dc.contributor.affiliationother | Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark | en_US |
dc.contributor.affiliationother | Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine (ICMM), The Panum Institute, University of Copenhagen, Copenhagen, Denmark | en_US |
dc.contributor.affiliationother | Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia | en_US |
dc.contributor.affiliationother | Department of Biology, Gallaudet University, Washington DC | en_US |
dc.contributor.affiliationother | Department of Biology, Gallaudet University, Washington DC | en_US |
dc.contributor.affiliationother | Department of Biology, Gallaudet University, Washington DC | en_US |
dc.contributor.affiliationother | UCL Institute of Child Health, London, UK | en_US |
dc.contributor.affiliationother | Departments of Ophthalmology and Surgery, Feinberg School of Medicine, Northwestern University, Evanston, Illinois | en_US |
dc.contributor.affiliationother | Division of Child and Adolescent Health, Department of Medical Genetics, University Hospital of North Norway, Tromsø, Norway | en_US |
dc.contributor.affiliationother | Department of Ophthalmology, Lundby Hospital, Gothenburg, Sweden | en_US |
dc.contributor.affiliationother | Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine (ICMM), The Panum Institute, University of Copenhagen, Copenhagen, Denmark | en_US |
dc.contributor.affiliationother | Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden | en_US |
dc.contributor.affiliationother | Department of Audiology/Disability Research (SIDR), Örebro University, Sweden | en_US |
dc.contributor.affiliationother | Department of Audiology, County Hospital, Kalmar, Sweden | en_US |
dc.contributor.affiliationother | Department of Psychiatrics, Stockholm, Sweden | en_US |
dc.contributor.affiliationother | Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine (ICMM), The Panum Institute, University of Copenhagen, Copenhagen, Denmark ; Department of Audiology, Bispebjerg Hospital, Copenhagen, Denmark ; Professor of Medical Genetics and Genetic Audiology. ; Department of Audiology, H:S Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/84383/1/33970_ftp.pdf | |
dc.identifier.doi | 10.1002/ajmg.a.33970 | en_US |
dc.identifier.source | American Journal of Medical Genetics Part A | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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