A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism

Cangul H., AYCAN Z., Kendall M., Bas V. N., Saglam Y., Barrett T. G., ...Daha Fazla

JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, cilt.27, sa.3-4, ss.323-327, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 3-4
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1515/jpem-2013-0314
  • Dergi Adı: JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.323-327
  • Anahtar Kelimeler: congenital hypothyroidism, DUOX2, mutation, thyroid dyshormonogenesis, CONSANGUINEOUS FAMILIES, TSHR MUTATIONS, NADPH OXIDASE, GOITER, GENETICS, PHENOMICS, DEFECTS, CLONING, LOCUS
  • Ankara Üniversitesi Adresli: Hayır

Özet

Mutations in DUOX2 have been reported to cause congenital hypothyroidism (CH), and our aim in this study was to determine the genetic basis of CH in two affected individuals coming from a consanguineous family. Because CH is usually inherited in autosomal recessive manner in consanguineous/ multicase families, we adopted a twostage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus using microsatellite markers and then screened for mutations in linked genes by Sanger sequencing. The family showed potential linkage to DUOX2 locus and we detected a nonsense mutation (R434X) in both cases and the mutation segregated with disease status in the family. This study highlights the importance of molecular genetic studies in the definitive diagnosis and classification of CH, and it also suggests a new clinical testing strategy using next-generation sequencing in all primary CH cases.