Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.
The Molecular Genetic Diagnosis Center, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China.
Growth Horm IGF Res. 2021 Oct-Dec;60-61:101423. doi: 10.1016/j.ghir.2021.101423. Epub 2021 Aug 3.
Isolated growth hormone deficiency (IGHD) due to mutations in GH1 gene is a rare disease caused by deficient production of endogenous growth hormone (GH).
We reported the clinical manifestation and genetic diagnosis (whole exome sequencing [WES], nested PCR Sanger sequencing, and rtPCR) of a family with two children with IGHD type I. We conducted a systematic review of cases with IGHD and compared height, and treatment outcomes in subtypes of IGHD.
The patients were siblings born of nonconsanguineous parents from the Chinese Han population. The siblings both presented significantly short stature without other apparent abnormalities. The patients carry compound heterozygous mutations in GH1: a deletion and c.456 + 1G > A mutation that led to abnormal splicing. The systematic review identified 365 IGHD cases with GH1 mutations. Among these patients, their body height was most severely impaired in patients with IGHD type Ia, and the height standard deviation score decreased with the age of diagnosis in IGHD type Ia. Patients with IGHD type II had the longest duration of rhGH treatment, while patients with IGHD type Ib had the highest relative height improvement.
We identified two patients with IGHD type I caused by compound heterozygotic GH1 deletion and splicing mutation. The analysis of previously published IGHD patients suggests differences in linear growth among subtypes of IGHD.
由于 GH1 基因突变导致的孤立性生长激素缺乏症（IGHD）是一种由内源性生长激素（GH）产生不足引起的罕见疾病。
我们报告了一个有两个 IGHD Ⅰ型患儿的家族的临床表现和遗传诊断（全外显子组测序[WES]、巢式 PCR Sanger 测序和 rtPCR）。我们对 IGHD 病例进行了系统回顾，并比较了 IGHD 各亚型的身高和治疗结果。
患者为非近亲汉族同胞兄妹，均表现为明显身材矮小，无其他明显异常。患者携带 GH1 的复合杂合突变：缺失和 c.456+1G>A 突变导致异常剪接。系统回顾共纳入 365 例 GH1 基因突变导致的 IGHD 病例。在这些患者中，IGHD Ⅰa 型患者的身高受损最严重，IGHD Ⅰa 型患者的身高标准差评分随诊断年龄的增加而降低。IGHD Ⅱ型患者的 rhGH 治疗时间最长，而 IGHD Ⅰb 型患者的相对身高改善最高。
我们发现了两例由 GH1 缺失和剪接突变引起的 IGHD Ⅰ型患者。对先前发表的 IGHD 患者的分析表明，IGHD 各亚型的线性生长存在差异。
