Open AccessVariations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss
Author(s) -
Güney Bademci,
Filiz Başak Cengiz,
Joseph Foster,
Duygu Duman,
Levent Sennaroğlu,
Oscar DiazHorta,
Tahir Atik,
Tayfun Kirazlı,
Levent Olgun,
Hüdaver Alper,
Ibis Menéndez,
İlayda Loçlar,
Gonca Sennaroğlu,
Suna Tokgöz-Yılmaz,
Shengru Guo,
Yüksel Olgun,
Nejat Mahdieh,
Mortaza Bonyadi,
Nazım Bozan,
Abdurrahman Ayral,
Ferda Özkınay,
Muzeyyen Yildirim-Baylan,
Susan H. Blanton,
Mustafa Tekin
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep31622
Subject(s) - sox10 , microphthalmia associated transcription factor , proband , genetics , ptpn11 , waardenburg syndrome , exome sequencing , biology , hearing loss , genetic heterogeneity , gene , medicine , mutation , audiology , phenotype , transcription factor , kras
The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes ( SOX10, MITF , PTPN11 , CHD7 , and KMT2D ) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg ( SOX10 and MITF ), Kallmann ( CHD7 and SOX10 ), Noonan/LEOPARD ( PTPN11 ), CHARGE ( CHD7 ), or Kabuki ( KMT2D ). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.