Sano Shinichiro, Masunaga Yohei, Kato Fumiko, Fujisawa Yasuko, Saitsu Hirotomo, Ogata Tsutomu
Department of Pediatric Endocrinology and Metabolism, Shizuoka Children's Hospital, Shizuoka, Japan.
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Clin Pediatr Endocrinol. 2022;31(3):172-177. doi: 10.1297/cpe.2022-0020. Epub 2022 Apr 23.
Recent studies have indicated that heterozygous loss-of-function variants in fibroblast growth factor receptor 1 () are involved in the development of congenital hypogonadotropic hypogonadism and combined pituitary hormone deficiency (CPHD). We encountered a Japanese boy with short stature and pubertal failure. Endocrine studies showed GH, TSH, and LH/FSH deficiencies, and brain magnetic resonance imaging delineated hypoplastic anterior pituitary and ectopic posterior pituitary. The patient was treated with GH, -thyroxine, and hCG/rFSH. Next-generation sequencing panel for pituitary dysfunction identified a probably weak disease-associated heterozygous missense variant in (NM_023110.3:c.176A>T:p.(Asp59Val)), together with a probably non-deleterious heterozygous missense variant in (NM_032551.5:c.769G>C:p.(Val257Leu)). We also review six previously reported CHPD patients with probably deleterious variants. The data, in conjunction with the previously reported cases, argue for the relevance of variants to the development of CPHD.
近期研究表明，成纤维细胞生长因子受体1（FGFR1）的杂合功能丧失变异与先天性低促性腺激素性性腺功能减退和联合垂体激素缺乏症（CPHD）的发生有关。我们遇到了一名身材矮小且青春期发育迟缓的日本男孩。内分泌检查显示生长激素（GH）、促甲状腺激素（TSH）以及促黄体生成素/促卵泡生成素（LH/FSH）缺乏，脑部磁共振成像显示垂体前叶发育不全和垂体后叶异位。该患者接受了生长激素、左甲状腺素以及人绒毛膜促性腺激素/重组促卵泡生成素（hCG/rFSH）治疗。针对垂体功能障碍的二代测序分析发现，FGFR1（NM_023110.3:c.176A>T:p.(Asp59Val)）存在一个可能与疾病相关的弱杂合错义变异，同时，另一个基因（NM_032551.5:c.769G>C:p.(Val257Leu)）存在一个可能无有害影响的杂合错义变异。我们还回顾了6例之前报道的携带可能有害的FGFR1变异的CPHD患者。这些数据，结合之前报道的病例，证明了FGFR1变异与CPHD发生的相关性。
