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Whole exome sequencing unravels disease‐causing genes in consanguineous families in Qatar
Author(s) -
Fahiminiya S.,
Almuriekhi M.,
Nawaz Z.,
Staffa A.,
Lepage P.,
Ali R.,
Hashim L.,
Schwartzentruber J.,
Abu Khadija K.,
Zaineddin S.,
Gamal H.,
Majewski J.,
BenOmran T.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12280
Subject(s) - proband , exome sequencing , genetics , consanguinity , nonsense mutation , sanger sequencing , biology , disease gene identification , compound heterozygosity , noonan syndrome , medical genetics , mutation , exome , gene , medicine , missense mutation
Whole exome sequencing ( WES ) has greatly facilitated the identification of causal mutations for diverse human genetic disorders. We applied WES as a molecular diagnostic tool to identify disease‐causing genes in consanguineous families in Qatar. Seventeen consanguineous families with diverse disorders were recruited. Initial mutation screening of known genes related to the clinical diagnoses did not reveal the causative mutations. Using WES approach, we identified the definitive disease‐causing mutations in four families: (i) a novel nonsense homozygous (c. 1034C >G) in PHKG2 causing glycogen storage disease type 9C ( GSD9C ) in a male with initial diagnosis of GSD3 ; (ii) a novel homozygous 1‐bp deletion (c.915del) in NSUN2 in a male proband with Noonan‐like syndrome; (iii) a homozygous SNV (c. 1598C >G) in exon 11 of IDUA causing Hurler syndrome in a female proband with unknown clinical diagnosis; (iv) a de novo known splicing mutation (c.1645+ 1G >A) in PHEX in a female proband with initial diagnosis of autosomal recessive hypophosphatemic rickets. Applying WES as a diagnostic tool led to the unambiguous identification of disease‐causing mutations in phenotypically complex disorders or correction of the initial clinical diagnosis in ˜25% of our cases.