TY - JOUR
T1 - A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism
AU - Cangul, Hakan
AU - Aycan, Zehra
AU - Kendall, Michaela
AU - Bas, Veysel N.
AU - Saglam, Yaman
AU - Barrett, Timothy G.
AU - Maher, Eamonn R.
PY - 2014/3/1
Y1 - 2014/3/1
N2 - 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 two-stage 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.
AB - 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 two-stage 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.
KW - congenital hypothyroidism
KW - DUOX2
KW - mutation
KW - thyroid dyshormonogenesis
UR - http://www.scopus.com/inward/record.url?scp=84896760996&partnerID=8YFLogxK
UR - https://www.degruyter.com/document/doi/10.1515/jpem-2013-0314/html
U2 - 10.1515/jpem-2013-0314
DO - 10.1515/jpem-2013-0314
M3 - Article
C2 - 24127536
AN - SCOPUS:84896760996
SN - 0334-018X
VL - 27
SP - 323
EP - 327
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 3-4
ER -