Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Chow Yock Ping, Nor Azian Abdul Murad, Zamzureena Mohd Rani, Jia Shiun Khoo, Pei Sin Chong, Loo Ling Wu, A. Rahman A. Jamal

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number40
JournalOrphanet Journal of Rare Diseases
Volume12
Issue number1
DOIs
Publication statusPublished - 21 Feb 2017
Externally publishedYes

Fingerprint

Exome
Siblings
Mutation
Deafness
Goiter
Parents
Bilateral Hearing Loss
Genes
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Sensorineural Hearing Loss
Hypothyroidism
Nuclear Family
Fathers
Computer Simulation
Pendred syndrome
Thyroid Gland
Mothers

Keywords

  • Autosomal recessive inheritance
  • Childhood deafness
  • Exome sequencing
  • Pendred syndrome
  • Syndromic hearing loss

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

@article{4544f003e72340b386d8a14a78a5a939,
title = "Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family",
abstract = "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.",
keywords = "Autosomal recessive inheritance, Childhood deafness, Exome sequencing, Pendred syndrome, Syndromic hearing loss",
author = "{Yock Ping}, Chow and {Abdul Murad}, {Nor Azian} and {Mohd Rani}, Zamzureena and Khoo, {Jia Shiun} and Chong, {Pei Sin} and Wu, {Loo Ling} and {A. Jamal}, {A. Rahman}",
year = "2017",
month = "2",
day = "21",
doi = "10.1186/s13023-017-0575-7",
language = "English",
volume = "12",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central",
number = "1",

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TY - JOUR

T1 - Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

AU - Yock Ping, Chow

AU - Abdul Murad, Nor Azian

AU - Mohd Rani, Zamzureena

AU - Khoo, Jia Shiun

AU - Chong, Pei Sin

AU - Wu, Loo Ling

AU - A. Jamal, A. Rahman

PY - 2017/2/21

Y1 - 2017/2/21

N2 - 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.

AB - 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.

KW - Autosomal recessive inheritance

KW - Childhood deafness

KW - Exome sequencing

KW - Pendred syndrome

KW - Syndromic hearing loss

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U2 - 10.1186/s13023-017-0575-7

DO - 10.1186/s13023-017-0575-7

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VL - 12

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

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