Homozygosity for a null allele of the insulin receptor gene in a patient with leprechaunism

✍ Scribed by Jennifer Hone; Domenico Accili; Helen Psiachou; Jamie Alghband-Zadeh; Sally Mitton; Efrat Wertheimer; Leonard Sinclair; Simeon I. Taylor

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 600 KB
• Volume: 6
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380060105

✦ Synopsis

Communicated by Urn Frrmcke

Mutations in the insulin receptor gene can cause genetic syndromes associated with extreme insulin resistance. We have investigated a patient with leprechaunism (IeprechaudQatar-I) born of a consanguineous marriage. Postnatally, the proband had episodes of severe hypoglycemia and hyperinsuhernia, with blood glucose levels ranging from 0.9 to 9.9 mmoVL. The C peptide concentration with 1880 nmoVL, and the total insulin concentration was 1409 mU/L. The patient died outside the hospital at the age of four months. All 22 exons of the patient's insulin reseptor gene were screened for mutations using denaturing gradient gel electrophoresis. Thereafter, the nucleotide sequences of selected exons were determined directly. The patient was homozygous for a mutation in exon 13; thirteen base pairs were deleted and replaced by a 5 b.p. sequence. This mutation shifts the d i n g frame and introduces a premature chain termination codon downstream in exon 13. Thus, the mutant allele is predicted to be a null allele that encodes a truncated receptor lacking both transmembrane and tyrosine kinase domains. o 1995 Wiey-Li. Inc.