Hermanns Pia, Couch Robert, Leonard Norma, Klotz Cherise, Pohlenz Joachim
Department of Pediatrics, Johannes Gutenberg University Medical School, Mainz, Germany.
Horm Res Paediatr. 2014;82(3):201-5. doi: 10.1159/000362413. Epub 2014 Jul 8.
Isolated central congenital hypothyroidism (ICCH) is rare but important. Most ICCH patients are diagnosed later, which results in severe growth failure and intellectual disability.
We describe a boy with ICCH due to a large homozygous TSHβ gene deletion.
A 51-day-old male Turkish infant, whose parents were first cousins, was admitted for evaluation of prolonged jaundice. His clinical appearance was compatible with hypothyroidism. Venous thyrotropin (TSH) was undetectably low, with a subsequent low free T4 and a low free T3, suggestive of central hypothyroidism. Using different PCR protocols, we could not amplify both coding exons of the boy's TSHβ gene, which suggested a deletion. An array comparative genomic hybridization (aCGH) using specific probes around the TSHβ gene locus showed him to be homozygous for a 6-kb deletion spanning all exons and parts of the 5' untranslated region of the gene.
Infants who are clinically suspected of having hypothyroidism should be evaluated thoroughly, even if their TSH-based screening result is normal. In cases with ICCH and undetectably low TSH serum concentrations, a TSHβ gene deletion should be considered; aCGH should be performed when gene deletions are suspected. In such cases, PCR-based sequencing techniques give negative results.
孤立性中枢性先天性甲状腺功能减退症（ICCH）罕见但很重要。大多数ICCH患者诊断较晚，这会导致严重的生长发育迟缓及智力残疾。
我们描述一名因TSHβ基因大片段纯合缺失导致ICCH的男孩。
一名51日龄的土耳其男婴，其父母为近亲结婚，因长期黄疸入院评估。他的临床表现符合甲状腺功能减退症。静脉促甲状腺激素（TSH）低至检测不到，随后游离T4和游离T3也低，提示中枢性甲状腺功能减退症。使用不同的PCR方案，我们无法扩增该男孩TSHβ基因的两个编码外显子，提示存在缺失。使用围绕TSHβ基因座的特异性探针进行的阵列比较基因组杂交（aCGH）显示，他在一个跨越该基因所有外显子及部分5'非翻译区的6 kb缺失上为纯合子。
临床上怀疑患有甲状腺功能减退症的婴儿应进行全面评估，即使基于TSH的筛查结果正常。对于ICCH且TSH血清浓度低至检测不到的病例，应考虑TSHβ基因缺失；怀疑有基因缺失时应进行aCGH检测。在这种情况下，基于PCR的测序技术会得出阴性结果。
