A nonsense thyrotropin receptor gene mutation (R609X) is associated with congenital hypothyroidism and heart defects.

Abstract

Congenital hypothyroidism (CH), one of the most important preventable causes of mental retardation, is a clinical condition characterized by thyroid hormone deficiency in newborns. CH is most often caused by defects in thyroid development leading to thyroid dysgenesis. The thyroid-stimulating hormone receptor (TSHR) is the main known gene causing thyroid dysgenesis in consanguineous families with CH. In this study, we aim to determine the genetic alteration in a case with congenital hypothyroidism and heart defects coming from a consanguineous family. We utilized genetic linkage analysis and direct sequencing to achieve our aim. Our results revealed that the family showed linkage to the TSHR locus, and we detected a homozygous nonsense mutation (R609X) in the case. Apart from other cases with the same mutation, our case had accompanying cardiac malformations. Although cardiac malformations are not uncommon in sporadic congenital hypothyroidism, here, they are reported for the first time with R609X mutation in a familial case.

• Authors: Hakan Cangul, Veysel N Bas, Yaman Saglam, Michaela Kendall, Timothy G Barrett, Eamonn R Maher, Zehra Aycan
• Journal: Journal of pediatric endocrinology & metabolism : JPEM (J Pediatr Endocrinol Metab) Vol. 27 Issue 11-12 Pg. 1101-5 (Nov 2014) ISSN: 2191-0251 [Electronic] Germany
• PMID: 24945425 (Publication Type: Case Reports, Journal Article)

Chemical References

• Codon, Nonsense
• Receptors, Thyrotropin

Topics

• Base Sequence
• Codon, Nonsense (genetics)
• Congenital Hypothyroidism (complications, genetics, pathology)
• DNA Mutational Analysis
• Female
• Haplotypes (genetics)
• Heart Defects, Congenital (complications, genetics, pathology)
• Homozygote
• Humans
• Infant, Newborn
• Male
• Microsatellite Repeats
• Molecular Sequence Data
• Pedigree
• Prognosis
• Receptors, Thyrotropin (genetics)