# Isolated Growth Hormone Deficiency IA due to a Novel Homozygous Large Deletion ∼1.6 kb Spanning Exons 1–4 of GH1 Gene: A Case Report

## TL;DR

A male infant with growth hormone deficiency was found to have a novel genetic deletion in the GH1 gene, highlighting the importance of genetic testing for accurate diagnosis.

## Contribution

A novel homozygous 1.6 kb deletion spanning exons 1–4 of the GH1 gene is reported in a patient with IGHD IA.

## Key findings

- The patient exhibited clinical features consistent with IGHD IA, including growth delay and physical abnormalities.
- Whole exome sequencing and PCR confirmed a homozygous deletion in the GH1 gene in the patient.
- Parents were heterozygous carriers of the deletion, and the sibling had a homozygous wild-type GH1 gene.

## Abstract

Isolated growth hormone deficiency (IGHD) IA is inherited autosomal recessively and occurs due to GH1 gene deletions. This study emphasizes the importance of clinical diagnosis and molecular examination for detecting novel mutations to prevent misdiagnosis and to consider timely and appropriate management of the current and long‐term consequences of the defect, such as additional deficiencies. We report a male infant who initially presented with a growth delay (‐4SD) at 4 months old, and at 16 months old, was referred to our endocrinology department. Physical examination revealed developmental delay, macrocephaly, head lag, loose body, large head circumference, low and flat nasal bridge, forehead protuberance, three‐pronged fingers, shortness of the hands and feet joints, small palms and plantar, small penises, delayed tooth eruption, and disability to walk. His hormonal tests showed normal free T4 (14.08 pmol/L), upper limit TSH level (5.41 μIU/mL), normal random cortisol 8 AM (250.53 μg/mL), mild high ACTH level (79.6 pg/mL), low IGF1 (13.0) and fasting GH (0.03 ng/mL). GH (ng/mL) maximal response to the arginine test was < 0.05. Whole Exome Sequencing, Polymerase Chain Reaction (PCR), and Quantitative Real‐Time PCR were performed on a peripheral blood sample obtained from the patient. The infant was found to have a homozygous large deletion of approximately 1.6 kb spanning the GH1 gene, which contained exons 1–4 with an autosomal recessive inheritance and a heterozygous deletion of exons 1–4 of GH1 in the parents and homozygous wild‐type in the sibling. Novel mutations in the GH‐1 gene cluster are considered an important cause of idiopathic congenital IGHD. As a result, the role of gene sequencing, besides considering clinical features, should not be neglected.