Blackburn James, Sivasanker Banupriya, Ahmed Shahida, van Meijgaarden Birgit, Korbonits Marta, Gevers Evelien
Department of Paediatric Endocrinology and Diabetes, Barts Health NHS Trust, Royal London Hospital, Whitechapel, London E1 1BB, UK.
Centre for Endocrinology, Queen Mary University of London, London EC1M 6BQ, UK.
JCEM Case Rep. 2025 Mar 28;3(5):luaf033. doi: 10.1210/jcemcr/luaf033. eCollection 2025 May.
The main features of immunoglobulin superfamily, member 1 () deficiency are central hypothyroidism and macroorchidism. The phenotype can be variable and may include macrosomia, hypoprolactinemia, growth hormone (GH) secretory abnormalities, delayed puberty, and obesity. We describe a novel de novo nonsense pathogenic variant c.3343C > T, p.(Gln1115*) that localizes to the 12th and last immunoglobulin-like loop in the C-terminal domain of the protein. The patient was born in breech with a birth weight of 3.7 kg. At presentation aged 15 years, he had obesity, central hypothyroidism, reduced attention, macroorchidism with delayed adrenarche and pubertal development. There was evidence of transient biochemical GH deficiency with normoprolactinemia and a small pituitary on magnetic resonance imaging, although interpretation of dynamic GH testing was difficult due to poor adherence with levothyroxine. He continued growing without GH treatment, and after spontaneous puberty, insulin-like growth factor-1 concentration was high. At age 22 years, he was 190 cm (+1.9 SDS), 155.4 kg (body mass index 43.05), with 35 mL testes. The transient GH deficiency and normoprolactinemia support a role for in somatotroph function.
免疫球蛋白超家族成员1（）缺乏的主要特征是中枢性甲状腺功能减退和巨睾症。其表型可能具有变异性，可能包括巨大儿、低催乳素血症、生长激素（GH）分泌异常、青春期延迟和肥胖。我们描述了一种新的从头无义致病性变异c.3343C>T，p.（Gln1115*），该变异定位于该蛋白质C末端结构域的第12个也是最后一个免疫球蛋白样环。该患者臀位出生，出生体重3.7 kg。15岁就诊时，他患有肥胖症、中枢性甲状腺功能减退、注意力不集中、巨睾症伴肾上腺初现和青春期发育延迟。有证据表明存在短暂的生化性GH缺乏，催乳素水平正常，磁共振成像显示垂体较小，尽管由于左甲状腺素依从性差，动态GH检测的解读困难。他在未接受GH治疗的情况下持续生长，自发青春期后，胰岛素样生长因子-1浓度较高。22岁时，他身高190 cm（+1.9 SDS），体重155.4 kg（体重指数43.05），睾丸体积35 mL。短暂的GH缺乏和催乳素水平正常支持了在生长激素细胞功能中的作用。
