Congenital central hypothyroidism caused by a novel thyroid-stimulating hormone-beta subunit gene mutation in two siblings

Congenital central hypothyroidism (cch) is a very rare disease. alterations in pituitary development genes as well as mutations of immunoglobulin superfamily member 1 and transducin β-like protein 1 can result in cch and multiple pituitary hormone deficiencies. however,mutations of the thyrotropin-releasing hormone receptor or thyroid-stimulating hormone-beta (tshb) gene are responsible for isolated cch. in this paper,we present the cases of two siblings with a novel mutation of tshb. direct sequencing of the coding regions and exon/intron boundaries of the tshb gene revealed two homozygous nucleotides changes. one of them was c.40a>g (rs10776792) which is a very common variation that is also seen in healthy individuals,the other was c.94g>a at codon 32 of exon 2 which resulted in a change from glutamic acid to lysine (p.e32k). both patients were homozygous and the parents were heterozygous. © 2017 by turkish pediatric endocrinology and diabetes society.