GM05241

GM05241 Fibroblast

Description:

LEPRECHAUNISM
INSULIN RECEPTOR; INSR

Affected:

Yes

Sex:

Female

Age:

1 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Cell line Minn-1. Low birth weight; hirsutism, insulin resistant, characteristic facies, and no subcutaneous fat; normal number of insulin receptors with reduced affinity in fibroblasts; reduced number of receptors with normal affinity in lymphoblasts.

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

INSULIN RECEPTOR FUNCTION

Reddy et al (J Clin Invest 82:1359-1365,1988) reported fibroblasts from this patient showed <15% of control insulin binding, a reduced number of insulin receptors, normal percentage of bound insulin that is internalized & degraded, reduced amount of insulin receptor autophosphorylation when normalized to insulin binding, & decreased receptor-associated tyrosine kinase activity toward exogenous substrates.

Gene

INSR

Chromosomal Location

19p13.2

Allelic Variant 1

147670.0007; LEPRECHAUNISM MINN 1

Identified Mutation

ARG924TER; In a patient with leprechaunism, designated leprechaun Minn-1, Kadowaki et al. (1990) identified a nonsense mutation at codon 897 in exon 14 in the paternal allele of the patient's insulin receptor gene. In addition, they obtained evidence that the patient's maternal allele contained a cis-acting dominant mutation that, like the paternal allele, caused a decrease in the level of mRNA. The nucleotide sequence of the entire protein-coding domain and the sequences of the intron-exon boundaries of all 22 exons of the maternal allele were normal.

Phenotypic Data

Remarks

Publications

Iovino S, Burkart AM, Kriauciunas K, Warren L, Hughes KJ, Molla M, Lee YK, Patti ME, Kahn CR, Genetic insulin resistance is a potent regulator of gene expression and proliferation in human iPS cells Diabetes63:4130-42 2014

PubMed ID: 25059784

Goodman PA, Sbraccia P, Brunetti A, Wong KY, Carter JD, Rosenthal SM, Goldfine ID, Growth factor receptor regulation in the Minn-1 leprechaun: defects in both insulin receptor and epidermal growth factor receptor gene expression Metabolism: clinical and experimental41:504-9 1992

PubMed ID: 1316988

Kadowaki T, Kadowaki H, Taylor SI, A nonsense mutation causing decreased levels of insulin receptor mRNA: detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction Proceedings of the National Academy of Sciences of the United States of America87:658-62 1990

PubMed ID: 2300553

Reddy SS, Lauris V, Kahn CR, Insulin receptor function in fibroblasts from patients with leprechaunism. Differential alterations in binding, autophosphorylation, kinase activity, and receptor-mediated internalization. J Clin Invest82:1359-65 1988

PubMed ID: 3049675

Endo F, Nagata N, Priest JH, Longo N, Elsas LJ 2d, Structural analysis of normal and mutant insulin receptors in fibroblasts cultured from families with leprechaunism. Am J Hum Genet41:402-17 1987

PubMed ID: 3631076

Podskalny JM, Kahn CR, Cell culture studies on patients with extreme insulin resistance. I. Receptor defects on cultured fibroblasts. J Clin Endocrinol Metab54:261-8 1982

PubMed ID: 7033276

Podskalny JM, Kahn CR, Cell culture studies on patients with extreme insulin resistance. II. Abnormal biological responses in cultured fibroblasts. J Clin Endocrinol Metab54:269-75 1982

PubMed ID: 6798064

Taylor SI, Samuels B, Roth J, Kasuga M, Hedo JA, Gorden P, Brasel DE, Pokora T, Engel RR, Decreased insulin binding in cultured lymphocytes from two patients with extreme insulin resistance. J Clin Endocrinol Metab54:919-30 1982

PubMed ID: 7037823