Genetic causes of moderate to severe hearing loss point to modifiers

被引：41

作者：

Naz, S. ^{[1
]}

Imtiaz, A. ^{[1
,2
]}

Mujtaba, G. ^{[1
,5
]}

Maqsood, A. ^{[1
]}

Bashir, R. ^{[1
,6
]}

Bukhari, I. ^{[1
,7
]}

Khan, M. R. ^{[1
,8
]}

Ramzan, M. ^{[1
]}

Fatima, A. ^{[1
]}

Rehman, A. U. ^{[2
,9
]}

Iqbal, M. ^{[1
]}

Chaudhry, T. ^{[2
]}

Lund, M. ^{[2
]}

Brewer, C. C. ^{[3
]}

Morell, R. J. ^{[2
,4
]}

Friedman, T. B. ^{[2
]}

机构：

[1] Univ Punjab, Sch Biol Sci, Quaid I Azam Campus, Lahore 54590, Pakistan

[2] NIDCD, Lab Mol Genet, NIH, Bethesda, MD USA

[3] NIDCD, Audiol Unit, NIH, Bethesda, MD USA

[4] NIDCD, Genom & Computat Biol Core, NIH, Bethesda, MD USA

[5] Inst Nucl Med & Oncol INMOL, Lahore, Pakistan

[6] Lahore Coll Women Univ, Dept Biotechnol, Lahore, Pakistan

[7] King Saud Univ Riyadh, Dept Biochem, Riyadh, Saudi Arabia

[8] Univ Sci & Technol China, Sch Sci, Hefei, Anhui, Peoples R China

[9] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

来源：

CLINICAL GENETICS | 2017年 / 91卷 / 04期

基金：

美国国家卫生研究院;

关键词：

etiology; deafness; DFNB; hearing loss; modifiers; mutation; Pakistan; AUTOSOMAL RECESSIVE DEAFNESS; NONSYNDROMIC DEAFNESS; USHER-SYNDROME; MUTATION; IMPAIRMENT; FAMILY; PROFILE; MYO15A; PTPRQ; DFNB3;

D O I：

10.1111/cge.12856

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The genetic underpinnings of recessively inherited moderate to severe sensorineural hearing loss are not well understood, despite its higher prevalence in comparison to profound deafness. We recruited 92 consanguineous families segregating stable or progressive, recessively inherited moderate or severe hearing loss. We utilized homozygosity mapping, Sanger sequencing, targeted capture of known deafness genes with massively parallel sequencing and whole exome sequencing to identify the molecular basis of hearing loss in these families. Variants of the known deafness genes were found in 69% of the participating families with the SLC26A4, GJB2, MYO15A, TMC1, TMPRSS3, OTOF, MYO7A and CLDN14 genes together accounting for hearing loss in 54% of the families. We identified 20 reported and 21 novel variants in 21 known deafness genes; 16 of the 20 reported variants, previously associated with stable, profound deafness were associated with moderate to severe or progressive hearing loss in our families. These data point to a prominent role for genetic background, environmental factors or both as modifiers of human hearing loss severity.

引用

页码：589 / 598

页数：10

共 32 条

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