Oguma Makiko, Kobayashi Mizuki, Yamazaki Masayo, Yokoyama Koji, Morikawa Shuntaro, Yamaguchi Takeshi, Yamagata Takanori, Tajima Toshihiro
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Department of Pediatrics, Hokkaido University School of Medicine, Hokkaido, Japan.
Clin Pediatr Endocrinol. 2018;27(2):95-100. doi: 10.1297/cpe.27.95. Epub 2018 Apr 13.
Genetic defects in the immunoglobulin superfamily member 1(IGSF1) protein are the cause of congenital central hypothyroidism (C-CH). Here we report two Japanese siblings with C-CH due to a novel mutation. The youngest brother showed a failure to thrive, hypothermia, and neonatal icterus six days after birth. Further endocrine evaluations led to the diagnosis of C-CH. In addition, PRL deficiency was later detected. In contrast, the elder brother did not show symptoms of severe hypothyroidism during the neonatal period, but he had been followed up by doctors due to psychomotor developmental delays since the age of 1 yr. At the age of 3 yr, he had low thyroxine and PRL levels and was also diagnosed with C-CH. Because of the C-CH and PRL deficiency, an IGSF1 deficiency was suspected. Sequence analysis of the gene identified a novel hemizygous mutation of p.Trp1173GlyfsTer8 (NM_001170961.1:c.3517del) in both siblings. In conclusion, the phenotypic severity of C-CH is different, even in siblings. Importantly, an IGSF1 deficiency may result in severe hypothyroidism during the neonatal period.
免疫球蛋白超家族成员1（IGSF1）蛋白的基因缺陷是先天性中枢性甲状腺功能减退症（C-CH）的病因。在此，我们报告了两名因新突变而患有C-CH的日本兄弟姐妹。最小的弟弟出生六天后出现生长发育迟缓、体温过低和新生儿黄疸。进一步的内分泌评估导致了C-CH的诊断。此外，后来检测到催乳素缺乏。相比之下，哥哥在新生儿期未表现出严重甲状腺功能减退的症状，但自1岁起因精神运动发育迟缓而一直在接受医生随访。3岁时，他的甲状腺素和催乳素水平较低，也被诊断为C-CH。由于存在C-CH和催乳素缺乏，怀疑存在IGSF1缺乏。对该基因的序列分析在两名兄弟姐妹中均发现了一种新的半合子突变p.Trp1173GlyfsTer8（NM_001170961.1:c.3517del）。总之，即使是在兄弟姐妹中，C-CH的表型严重程度也有所不同。重要的是，IGSF1缺乏可能导致新生儿期严重甲状腺功能减退。
