TY - JOUR
T1 - An essential splice site mutation (c.317+1G>A) in the TSHR gene leads to severe thyroid dysgenesis
AU - Cangul, Hakan
AU - Saglam, Halil
AU - Saglam, Yaman
AU - Eren, Erdal
AU - Dogan, Durmus
AU - Kendall, Michaela
AU - Tarim, Omer
AU - Maher, Eamonn R.
AU - Barrett, Timothy G.
PY - 2014/9/20
Y1 - 2014/9/20
N2 - Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and 2% of cases have familial origin. Our aim in this study was to determine the genetic alterations in two siblings with CH coming from a consanguineous family. Because CH is often inherited in autosomal recessive manner in consanguineous/multicase-families, we first performed genetic linkage studies to all known causative CH loci followed by conventional sequencing of the linked gene. The family showed potential linkage to the TSHR locus, and we detected an essential splice site mutation (c.317+1G>A) in both siblings. RT-PCR analysis confirmed the functionality of the mutation. The mutation was homozygous in the cases whereas heterozygous in carrier parents and an unaffected sibling. Here we conclude that thyroid agenesis in both siblings in this study originates from c.317+1G>A splice site mutation in the TSHR gene, and this study underlines the importance of detailed molecular genetic studies in the definitive diagnosis and classification of CH.
AB - Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and 2% of cases have familial origin. Our aim in this study was to determine the genetic alterations in two siblings with CH coming from a consanguineous family. Because CH is often inherited in autosomal recessive manner in consanguineous/multicase-families, we first performed genetic linkage studies to all known causative CH loci followed by conventional sequencing of the linked gene. The family showed potential linkage to the TSHR locus, and we detected an essential splice site mutation (c.317+1G>A) in both siblings. RT-PCR analysis confirmed the functionality of the mutation. The mutation was homozygous in the cases whereas heterozygous in carrier parents and an unaffected sibling. Here we conclude that thyroid agenesis in both siblings in this study originates from c.317+1G>A splice site mutation in the TSHR gene, and this study underlines the importance of detailed molecular genetic studies in the definitive diagnosis and classification of CH.
KW - congenital hypothyroidism
KW - gene
KW - mutation
KW - splicing
KW - thyroid dysgenesis, genetics
KW - TSHR
UR - http://www.scopus.com/inward/record.url?scp=84906981161&partnerID=8YFLogxK
UR - https://www.degruyter.com/document/doi/10.1515/jpem-2014-0048/html
U2 - 10.1515/jpem-2014-0048
DO - 10.1515/jpem-2014-0048
M3 - Article
C2 - 24859513
AN - SCOPUS:84906981161
SN - 0334-018X
VL - 27
SP - 1021
EP - 1025
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 9-10
ER -