[GH receptor gene mutations and growth failure]

Area of Science:

• Endocrinology
• Human Genetics
• Molecular Biology

Context:

• Primary growth hormone (GH) insensitivity often stems from abnormalities in the GH receptor (GHR) and its signal transduction pathways.
• Over 30 distinct GHR gene mutations, primarily homozygous, have been identified in Laron syndrome patients.
• Heterozygous mutations are observed in some individuals with idiopathic short stature.

Purpose:

• To review the diverse clinical and molecular characteristics of abnormal GHR genes in patients with GH insensitivity.
• To present a case of Laron syndrome caused by novel compound heterozygous mutations.
• To describe familial short stature associated with high serum GHBP levels due to a heterozygous GHR splice site mutation.

Summary:

• Abnormalities in the growth hormone receptor (GHR) gene and signal transduction are key causes of primary GH insensitivity.
• Analysis reveals numerous GHR gene mutations, including homozygous forms in Laron syndrome and heterozygous forms in idiopathic short stature.
• This review details varied clinical and molecular GHR gene findings, featuring a Laron syndrome case with novel compound heterozygous mutations and familial short stature linked to a splice site mutation.

Impact:

• Advances understanding of the genetic basis of GH insensitivity.
• Highlights the clinical and molecular spectrum of GHR gene mutations.
• Provides insights into diagnosing and managing rare growth disorders.