Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients

被引：67

作者：

Baux, D. ^{[1
]}

Vache, C. ^{[1
]}

Blanchet, C. ^{[2
,3
]}

Willems, M. ^{[4
]}

Baudoin, C. ^{[1
]}

Moclyn, M. ^{[1
]}

Faugere, V. ^{[1
]}

Touraine, R. ^{[5
]}

Isidor, B. ^{[6
]}

Dupin-Deguine, D. ^{[7
,8
]}

Nizon, M. ^{[6
]}

Vincent, M. ^{[6
]}

Mercier, S. ^{[6
]}

Calais, C. ^{[9
]}

Garcia-Garcia, G. ^{[10
]}

Azher, Z. ^{[10
]}

Lambert, L. ^{[11
]}

Perdomo-Trujillo, Y. ^{[12
]}

Giuliano, F. ^{[13
]}

Claustres, M. ^{[1
,10
]}

Koenig, M. ^{[1
,10
]}

Mondain, M. ^{[2
,3
]}

Roux, A. F. ^{[1
,10
]}

机构：

[1] CHU Montpellier, Lab Genet Mol, Montpellier, France

[2] CHU Montpellier, Serv ORL, Montpellier, France

[3] CHU Montpellier, Ctr Natl Reference Malad Rares Affect Sensorielle, Montpellier, France

[4] CHU Montpellier, Genet Med, Montpellier, France

[5] CHU Hop Nord, Serv Genet, St Etienne, France

[6] CHU Nantes, Serv Genet Med, Nantes, France

[7] CHU Toulouse, Serv Genet Med, Toulouse, France

[8] CHU Toulouse, Serv ORL, Otoneurol & ORL Pediat, Toulouse, France

[9] CHU Nantes, Serv ORL, Nantes, France

[10] Univ Montpellier, LGMR, EA7402, Montpellier, France

[11] CHRU Nancy, Genet Med, Ctr Competence Surdites Genet, Site Constitutif Ctr Reference Anomalies Dev & Sy, Nancy, France

[12] Hop Civil, Ctr Reference Affect Rares Genet Ophtalmol CARGO, Serv Genet Med, Strasbourg, France

[13] CHU Nice, Serv Genet Med, Nice, France

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

GENOTYPE-PHENOTYPE CORRELATION; USHER-SYNDROME; SYNDROMIC DEAFNESS; MUTATIONS; VARIANTS; FAMILIES; UPDATE; ACTG1;

D O I：

10.1038/s41598-017-16846-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hearing loss is the most common sensory disorder and because of its high genetic heterogeneity, implementation of Massively Parallel Sequencing (MPS) in diagnostic laboratories is greatly improving the possibilities of offering optimal care to patients. We present the results of a two-year period of molecular diagnosis that included 207 French families referred for non-syndromic hearing loss. Our multi-step strategy involved (i) DFNB1 locus analysis, (ii) MPS of 74 genes, and (iii) additional approaches including Copy Number Variations, in silico analyses, minigene studies coupled when appropriate with complete gene sequencing, and a specific assay for STRC. This comprehensive screening yielded an overall diagnostic rate of 48%, equally distributed between DFNB1 (24%) and the other genes (24%). Pathogenic genotypes were identified in 19 different genes, with a high prevalence of GJB2, STRC, MYO15A, OTOF, TMC1, MYO7A and USH2A. Involvement of an Usher gene was reported in 16% of the genotyped cohort. Four de novo variants were identified. This study highlights the need to develop several molecular approaches for efficient molecular diagnosis of hearing loss, as this is crucial for genetic counselling, audiological rehabilitation and the detection of syndromic forms.

引用

页数：10

共 38 条

[31] Usher Syndrome Type 2 Caused by Activation of an USH2A Pseudoexon: Implications for Diagnosis and Therapy [J].

Vache, Christel ;

Besnard, Thomas ;

le Berre, Pauline ;

Garcia-Garcia, Gema ;

Baux, David ;

Larrieu, Lise ;

Abadie, Caroline ;

Blanchet, Catherine ;

Bolz, Hanno Joern ;

Millan, Jose ;

Hamel, Christian ;

Malcolm, Sue ;

Claustres, Mireille ;

Roux, Anne-Francoise .

HUMAN MUTATION, 2012, 33 (01) :104-108

[32]

Van Camp G., 2008, HEREDITARY HEARING L

[33] DFNB16 is a frequent cause of congenital hearing impairment: implementation of STRC mutation analysis in routine diagnostics [J].

Vona, B. ;

Hofrichter, M. A. H. ;

Neuner, C. ;

Schroeder, J. ;

Gehrig, A. ;

Hennermann, J. B. ;

Kraus, F. ;

Shehata-Dieler, W. ;

Klopocki, E. ;

Nanda, I. ;

Haaf, T. .

CLINICAL GENETICS, 2015, 87 (01) :49-55

[34] Genotype-Phenotype Correlation in DFNB8/10 Families with TMPRSS3 Mutations [J].

Weegerink, Nicole J. D. ;

Schraders, Margit ;

Oostrik, Jaap ;

Huygen, Patrick L. M. ;

Strom, Tim M. ;

Granneman, Susanne ;

Pennings, Ronald J. E. ;

Venselaar, Hanka ;

Hoefsloot, Lies H. ;

Elting, Mariet ;

Cremers, Cor W. R. J. ;

Admiraal, Ronald J. C. ;

Kremer, Hannie ;

Kunst, Henricus P. M. .

JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY, 2011, 12 (06) :753-766

[35] Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents [J].

Yan, Denise ;

Tekin, Demet ;

Bademci, Guney ;

Foster, Joseph, II ;

Cengiz, F. Basak ;

Kannan-Sundhari, Abhiraami ;

Guo, Shengru ;

Mittal, Rahul ;

Zou, Bing ;

Grati, Mhamed ;

Kabahuma, Rosemary I. ;

Kameswaran, Mohan ;

Lasisi, Taye J. ;

Adedeji, Waheed A. ;

Lasisi, Akeem O. ;

Menendez, Ibis ;

Herrera, Marianna ;

Carranza, Claudia ;

Maroofian, Reza ;

Crosby, Andrew H. ;

Bensaid, Mariem ;

Masmoudi, Saber ;

Behnam, Mahdiyeh ;

Mojarrad, Majid ;

Feng, Yong ;

Duman, Duygu ;

Mawla, Alex M. ;

Nord, Alex S. ;

Blanton, Susan H. ;

Liu, Xue Z. ;

Tekin, Mustafa .

HUMAN GENETICS, 2016, 135 (08) :953-961

[36] Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals [J].

Yeo, G ;

Burge, CB .

JOURNAL OF COMPUTATIONAL BIOLOGY, 2004, 11 (2-3) :377-394

[37] Evidence for genotype-phenotype correlation for OTOF mutations [J].

Yildirim-Baylan, Muzeyyen ;

Bademci, Guney ;

Duman, Duygu ;

Ozturkmen-Akay, Hatice ;

Tokgoz-Yilmaz, Suna ;

Tekin, Mustafa .

INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY, 2014, 78 (06) :950-953

[38] Mutations in the γ-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26) [J].

Zhu, M ;

Yang, T ;

Wei, S ;

DeWan, AT ;

Morell, RJ ;

Elfenbein, JL ;

Fisher, RA ;

Leal, SM ;

Smith, RJH ;

Friderici, KH .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (05) :1082-1091

← 1 2 3 4 →