Mutations in GH1 gene and isolated growth hormone deficiency (IGHD): A familial case of IGHD type I and systematic review

Background: Isolated growth hormone deficiency (IGHD) due to mutations in GH1 gene is a rare disease caused by deficient production of endogenous growth hormone (GH). Methods: 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. Results: 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. Conclusion: 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.

Automated summary

Two siblings from a nonconsanguineous Chinese Han family were diagnosed with IGHD type I due to compound heterozygous mutations in GH1, involving a deletion and a splicing mutation. A systematic review of published cases revealed that patients with IGHD type Ia had the most severely impaired height, and their height standard deviation score decreased with age at diagnosis. Patients with IGHD type II received the longest duration of rhGH treatment, while those with IGHD type Ib showed the highest relative height improvement.