Cangul Hakan, Bas Veysel N, Saglam Yaman, Kendall Michaela, Barrett Timothy G, Maher Eamonn R, Aycan Zehra
J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1101-5. doi: 10.1515/jpem-2014-0025.
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.
先天性甲状腺功能减退症（CH）是智力发育迟缓最重要的可预防病因之一，是一种以新生儿甲状腺激素缺乏为特征的临床病症。CH最常由甲状腺发育缺陷导致甲状腺发育不全引起。促甲状腺激素受体（TSHR）是已知的导致患有CH的近亲家庭中甲状腺发育不全的主要基因。在本研究中，我们旨在确定一个来自近亲家庭的先天性甲状腺功能减退症合并心脏缺陷病例的基因改变。我们利用基因连锁分析和直接测序来实现我们的目标。我们的结果显示该家族与TSHR基因座连锁，并且我们在该病例中检测到一个纯合无义突变（R609X）。除了其他具有相同突变的病例外，我们的病例伴有心脏畸形。虽然心脏畸形在散发性先天性甲状腺功能减退症中并不罕见，但在此，它们首次在一个家族性病例中与R609X突变一起被报道。
