Eisenberger, Tobias, Di Donato, Nataliya ORCID: 0000-0001-9439-4677, Baig, Shahid M., Neuhaus, Christine, Beyer, Anke, Decker, Eva, Muerbe, Dirk, Decker, Christian, Bergmann, Carsten and Bolz, Hanno J. (2014). Targeted and Genomewide NGS Data Disqualify Mutations in MYO1A, the DFNA48 Gene, as a Cause of Deafness. Hum. Mutat., 35 (5). S. 565 - 571. HOBOKEN: WILEY. ISSN 1098-1004

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Abstract

MYO1A is considered the gene underlying autosomal dominant nonsyndromic hearing loss DFNA48, based on six missense variants, one small in-frame insertion, and one nonsense mutation. Results from NGS targeting 66 deafness genes in 109 patients identified three families challenging this assumption: two novel nonsense (p.Tyr740* and p.Arg262*) and a known missense variant were identified heterozygously not only in index patients, but also in unaffected relatives. Deafness in these families clearly resulted from mutations in other genes (MYO7A, EYA1, and CIB2). Most of the altogether 10 MYO1A mutations are annotated in dbSNP, and population frequencies (dbSNP, 1000 Genomes, Exome Sequencing Project) above 0.1% contradict pathogenicity under a dominant model. One healthy individual was even homozygous for p.Arg262*, compatible with homozygous Myo1a knockout mice lacking any overt pathology. MYO1A seems dispensable for hearing and overall nonessential. MYO1A adds to the list of erroneous disease genes, which will expand with increasing availability of large-scale sequencing data.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Eisenberger, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Donato, NataliyaUNSPECIFIEDorcid.org/0000-0001-9439-4677UNSPECIFIED
Baig, Shahid M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhaus, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, AnkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Decker, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muerbe, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Decker, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergmann, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolz, Hanno J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-439016
DOI: 10.1002/humu.22532
Journal or Publication Title: Hum. Mutat.
Volume: 35
Number: 5
Page Range: S. 565 - 571
Date: 2014
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1098-1004
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BORDER MYOSIN IA; MESSENGER-RNA; EXOME DATA; PATHOGENICITY; SUBSTITUTIONS; CONSEQUENCES; PREDICTION; TOOLMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43901

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