Dataset Information

ENU induced single mutation locus on chr 16 leads to high-frequency hearing loss in mice.

ABSTRACT: The hallmark of age-related (presbycusis) and noise-induced hearing loss is high-frequency (> 20 kHz) hearing loss. Through a collaborative study with TMGC (Tennessee Mouse Genome Consortium), seventeen ENU-induced mouse mutation strains with high-frequency hearing loss have been identified, but affected genes are yet identified. As a first step in identifying the gene/s underlying the ENU mutations, we created a F2 population between a representative mutation strain, 118 TNE and a wild type strain, CAST/EJ (CAST). Phenotypic analysis showed that there is a 3:1 ratio of segregation between normal and hearing loss in the F2 population, suggestion a single locus regulation. However, the linkage mapping identified 2 QTLs, each on chromosomes 15 and 16. Further statistical analysis of marker segregation patterns revealed that the locus on Chr 16 was ENU induced while the one on Chr 15 was derived from the parental strain, CAST.

SUBMITTER: Jiao Y

PROVIDER: S-EPMC3155952 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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ENU induced single mutation locus on chr 16 leads to high-frequency hearing loss in mice.

Jiao Yan Y Cai Chun C Kermany Mohammad Habiby MH Yan Jian J Cai Qing Q Miller Darla D Goldowitz Daniel D Li Xinmin X Yoo Tai-June TJ Gu Weikuan W

Genes & genetic systems 20090601 3

The hallmark of age-related (presbycusis) and noise-induced hearing loss is high-frequency (> 20 kHz) hearing loss. Through a collaborative study with TMGC (Tennessee Mouse Genome Consortium), seventeen ENU-induced mouse mutation strains with high-frequency hearing loss have been identified, but affected genes are yet identified. As a first step in identifying the gene/s underlying the ENU mutations, we created a F2 population between a representative mutation strain, 118 TNE and a wild type str ...[more]

PMID: 19745570

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Project description:BackgroundTo date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL.MethodsSubjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling.ResultsPathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive.ConclusionsTECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

Dataset Information

ENU induced single mutation locus on chr 16 leads to high-frequency hearing loss in mice.

Publications

ENU induced single mutation locus on chr 16 leads to high-frequency hearing loss in mice.

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