Comprehensive Analysis Via Exome Sequencing Uncovers Genetic Etiology In Autosomal Recessive Non-Syndromic Deafness In A Large Multiethnic Cohort
Tarih
2016Yazar
Bademci, Guney
Foster, Joseph
Mahdieh, Nejat
Bonyadi, Mortaza
Duman, Duygu
Cengiz, F.Basak
Menendez, Ibis
Horta, Oscar Diaz
Shirkavand, Atefeh
Zeinali, Sirous
Subasioglu, Asli
Tokgoz-Yilmaz, Suna
Hernandez, Fabiola Huesca
de la Luz Arenas Sordo, Maria
Dominguez-Aburto, Juan
Hernandez-Zamora, Edgar
Montenegro, Paola
Paredes, Rosario
Moreta, Germania
Vinueza, Rodrigo
Villegas, Franklin
Mendoza Benitez, Santiago
Guo, Shengru
Bozan, Nazim
Tos, Tulay
Incesulu, Armagan
Sennaroglu, Gonca
Blanton, Susan H.
Ozturkmen Akay, Hatice
Yildirim-Baylan, Muzeyyen
Tekin, Mustafa
Üst veri
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Purpose Autosomal recessive non-syndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity with reported mutations in 58 different genes. This study was designed to detect deafness causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES). Methods After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador and Puerto Rico to screen for mutations in all known ARNSD genes. Results We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%) and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes suggesting founder effects. Conclusion We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.
Bağlantı
https://doi.org/10.1038/gim.2015.89https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733433/
http://hdl.handle.net/11655/20999