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- Title
Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family.
- Authors
Yock-Ping Chow; Abdul Murad, Nor Azian; Rani, Zamzureena Mohd; Jia-Shiun Khoo; Pei-Sin Chong; Loo-Ling Wu; Jamal, Rahman; Chow, Yock-Ping; Mohd Rani, Zamzureena; Khoo, Jia-Shiun; Chong, Pei-Sin; Wu, Loo-Ling
- Abstract
<bold>Background: </bold>Pendred syndrome (PDS, MIM #274600) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss and goiter. In this study, we describing the possible PDS causal mutations in a Malaysian family with 2 daughters diagnosed with bilateral hearing loss and hypothyroidism.<bold>Methods and Results: </bold>Whole exome sequencing was performed on 2 sisters with PDS and their unaffected parents. Our results showed that both sisters inherited monoallelic mutations in the 2 known PDS genes, SLC26A4 (ENST00000265715:c.1343C > T, p.Ser448Leu) and GJB2 (ENST00000382844:c.368C > A, p.Thr123Asn) from their father, as well as another deafness-related gene, SCARB2 (ENST00000264896:c.914C > T, p.Thr305Met) from their mother. We postulated that these three heterozygous mutations in combination may be causative to deafness, and warrants further investigation. Furthermore, we also identified a compound heterozygosity involving the DUOX2 gene (ENST00000603300:c.1588A > T:p.Lys530* and c.3329G > A:p.Arg1110Gln) in both sisters which are inherited from both parents and may be correlated with early onset of goiter. All the candidate mutations were predicted deleterious by in silico tools.<bold>Conclusions: </bold>In summary, we proposed that PDS in this family could be a polygenic disorder which possibly arises from a combination of heterozygous mutations in SLC26A4, GJB2 and SCARB2 which associated with deafness, as well as compound heterozygous DUOX2 mutations which associated with thyroid dysfunction.
- Subjects
MALAYSIA; PENDRED syndrome; HYPOTHYROIDISM; GENETICS of deafness; FAMILY health; HYPOTHYROIDISM diagnosis; GENETIC mutation; PUBLIC health; GENETICS; DIAGNOSIS
- Publication
Orphanet Journal of Rare Diseases, 2017, Vol 12, p1
- ISSN
1750-1172
- Publication type
journal article
- DOI
10.1186/s13023-017-0575-7