Systematic Review and Case Study Reveals Differences in IGHD Subtypes

A systematic review and case study of patients with isolated growth hormone deficiency (IGHD) due to mutations in GH1 gene suggests differences and linear growth among subtypes of isolated growth hormone deficiency (IGHD). Qiuyue Li and colleagues published these results in Growth Hormone & IGF Research.

“IGHD due to mutations in GH1 gene is a rare disease caused by deficient production of endogenous growth hormone (GH),” the authors wrote. In this report, the researchers described the clinical manifestation and genetic diagnosis (via whole exome sequencing [WES], nested polymerase chain reaction [PCR] Sanger sequencing, and real-time [rtPCR]) of a family with two children with IGHD type I. In addition, they conducted a systematic review of cases with IGHD and compared height and treatment outcomes in subtypes of IGHD.

The children were siblings born of nonconsanguineous parents from the Chinese Han population. Each child presented with significantly short stature without other apparent abnormalities. Sequencing revealed that the patients carried compound heterozygous mutations in GH1: a deletion and c.456 + 1G > A that was linked to abnormal splicing.

The subsequent systematic review identified 365 IGHD cases with GH1 mutations. Height was most severely impaired in patients with IGHD type Ia, and progressively decreased with the age of diagnosis. However, short stature was less severe in IGHD type Ib and II, and among patients who had the longest duration of GH treatment. 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 authors wrote. “The analysis of previously published IGHD patients suggests differences in linear growth among subtypes of IGHD.”