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Homozygosity for a null allele of the insulin receptor gene in a patient with leprechaunism
Author(s) -
Hone Jennifer,
Accili Domenico,
Psiachou Helen,
AlghbandZadeh Jamie,
Mitton Sally,
Wertheimer Efrat,
Sinclair Leonard,
Taylor Simeon I.
Publication year - 1995
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380060105
Subject(s) - biology , exon , proband , insulin receptor , allele , mutation , stop codon , genetics , endocrinology , medicine , null allele , gene , insulin resistance , insulin , microbiology and biotechnology
Abstract Mutations in the insulin receptor gene can cause genetic syndromes associated with extreme insulin resistance. We have investigated a patient with leprechaunism (leprechaun/Qatar‐1) born of a consanguineous marriage. Postnatally, the proband had episodes of severe hypoglycemia and hyperinsulinernia, with blood glucose levels ranging from 0.9 to 9.9 mmol/L. The C peptide concentration with 1880 nmol/L, 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 reading frame and introduces a premature chain termination codon downstream in exon 13. Thus, the mutantallele is predicted to be a null allele that encodes a truncated receptor lacking both transmembrane and tyrosine kinase domains. © 1995 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.