GM20328

GM20328 Fibroblast from Skin, Unspecified

Description:

LEPRECHAUNISM
INSULIN RECEPTOR; INSR

Affected:

Yes

Sex:

Male

Age:

2 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Race

White

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; birth weight 1,590 g at 42 weeks gestation (<5th percentile); hirsutism; acanthosis nigricans; peripheral edema; thickened lips; prominent nipples; disproportionately large genitalia; heart murmur; developmental delay; failure to thrive; severe constipation; recurrent upper respiratory tract infections; died at 26 months; autopsy revealed: severe pulmonary hypertension, moderate concentric bilateral hypertrophy of heart, focal areas of proliferation of bile ducts, and hepatocytes contained PAS positive granules; fasting hypoglycemia and postprandial hyperglycemia with elevated levels of circulating insulin (1,200 uU/ml) noted in neonatal period; specific binding of insulin (to fibroblasts) = 0.02 +/- 0.02 (fmol/mg cell protein) with normal range being 1.01 - 2.20; donor subject is a compound heterozygote: one allele has an in-frame deletion of three nucleotides resulting in the deletion of codon 281 in exon 3 of the INSR gene [del c.1159-1161, N281] and a second allele has a G>A transition in the first nucleotide of the splice-donor junction in intron 13 of the INSR gene resulting in an in-frame deletion of amino acids 859-867 [IVS 13+1, G>A].

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

INSR

Chromosomal Location

19p13.2

Allelic Variant 1

; LEPRECHAUNISM

Identified Mutation

3-BP DEL (N281)

Gene

INSR

Chromosomal Location

19p13.2

Allelic Variant 2

; LEPRECHAUNISM

Identified Mutation

IVS13+1,G>A

Phenotypic Data

Remarks

Publications

Longo N, Wang Y, Smith SA, Langley SD, DiMeglio LA, Giannella-Neto D, Genotype-phenotype correlation in inherited severe insulin resistance. Hum Mol Genet11(12):1465-75 2002

PubMed ID: 12023989

Longo N, Langley SD, Griffin LD, Elsas LJ, Two mutations in the insulin receptor gene of a patient with leprechaunism: application to prenatal diagnosis. J Clin Endocrinol Metab80(5):1496-501 1995

PubMed ID: 7538143