Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family.
In: Orphanet Journal of Rare Diseases, Jg. 12 (2017-02-21), S. 1-9
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Zugriff:
Background: 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. Methods and Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]
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Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family.
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Autor/in / Beteiligte Person: | Chow, Yock-Ping ; Abdul Murad, Nor Azian ; Rani, Zamzureena Mohd ; Khoo, Jia-Shiun ; Chong, Pei-Sin ; Wu, Loo-Ling ; Jamal, Rahman ; Mohd Rani, Zamzureena |
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Zeitschrift: | Orphanet Journal of Rare Diseases, Jg. 12 (2017-02-21), S. 1-9 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
ISSN: | 1750-1172 (print) |
DOI: | 10.1186/s13023-017-0575-7 |
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