Department of Internal Medicine-Endocrinology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
Academic Center for Growth Disorders, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
Genes (Basel). 2022 Mar 30;13(4):623. doi: 10.3390/genes13040623.
In recent years, variants in immunoglobulin superfamily member 1 (IGSF1) have been associated with congenital hypopituitarism. Initially, IGSF1 variants were only reported in patients with central hypothyroidism (CeH) and macroorchidism. Later on, IGSF1 variants were also reported in patients with additional endocrinopathies, sometimes without macroorchidism. We studied IGSF1 as a new candidate gene for patients with combined CeH and growth hormone deficiency (GHD). We screened 80 male and 14 female Dutch patients with combined CeH and GHD for variants in the extracellular region of IGSF1, and we report detailed biomedical and clinical data of index cases and relatives. We identified three variants in our patient cohort, of which two were novel variants of unknown significance (p.L570I and c.1765+37C>A). In conclusion, we screened 94 patients with CeH and GHD and found variants in IGSF1 of which p.L570I could be of functional relevance. We provide detailed phenotypic data of two boys with the p.C947R variant and their large family. The remarkable phenotype of some of the relatives sheds new light on the phenotypic spectrum of IGSF1 variants.
近年来，免疫球蛋白超家族成员 1（IGSF1）的变异与先天性垂体功能减退症有关。最初，仅在中枢性甲状腺功能减退症（CeH）和巨大睾丸症的患者中报道 IGSF1 变异。后来，也在伴有其他内分泌疾病的患者中报道了 IGSF1 变异，有时没有巨大睾丸症。我们研究了 IGSF1 作为伴有 CeH 和生长激素缺乏症（GHD）的患者的新候选基因。我们对 80 名男性和 14 名女性荷兰伴有 CeH 和 GHD 的患者进行了 IGSF1 细胞外区域的变异筛选，并报告了索引病例和亲属的详细生物医学和临床数据。我们在患者队列中鉴定出了三种变异，其中两种是未知意义的新变异（p.L570I 和 c.1765+37C>A）。总之，我们对 94 名伴有 CeH 和 GHD 的患者进行了筛查，发现了 IGSF1 中的变异，其中 p.L570I 可能具有功能相关性。我们提供了两名携带 p.C947R 变异的男孩及其大家族的详细表型数据。一些亲属的显著表型为 IGSF1 变异的表型谱提供了新的认识。
