AG10587

AG10587 LCL from B-Lymphocyte

Description:

HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
LAMIN A/C; LMNA
NIA AGING CELL REPOSITORY DNA PANEL - AGING SYNDROMES

Affected:

Yes

Sex:

Male

Age:

9 YR (At Sampling)

Overview

Repository

NIA Aging Cell Culture Repository

Subcollection

Heritable Diseases

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

DUTCH

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

The donor displays the following clinical signs of progeria: alopecia, arthritis, skin changes, coxa valga, and angina. The donor has 6 times the normal level of hyaluronic acid in his urine. The blood specimen was taken ante-mortem on 6/27/89. Culture was initiated on 6/29/89 by transformation of lymphocytes with Epstein Barr virus. The cells grow in suspension and their morphology is spherical. Lymphoblast cultures from donor's unaffected brother and mother are AG10585 and AG10588, respectively. A skin fibroblast culture from same donor is AG10750. Donor subject has a de novo single base substitution, a C>T change at nucleotide 2036 (2036C>T), which results in a silent change at codon 608 [Gly608Gly (G608G)] in exon 11 of the Lamin A gene (LMNA). This substitution creates an exonic consensus splice donor sequence and results in activation of a cryptic splice site which in turn causes skipping of 150 bp of the LMNA mRNA leading to the deletion of 50 amino acids from the protein. This altered LMNA protein was detected on western blots [Eriksson et al., Nature 423:293 (2003)].

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Gene

LMNA

Chromosomal Location

1q21.2

Allelic Variant 1

150330.0022; HUTCHINSON-GILFORD PROGERIA SYNDROME

Identified Mutation

GLY608GLY; Description: In 18 of 20 patients with classic Hutchinson-Gilford progeria syndrome (176670), Eriksson et al. [Nature 423: 293 (2003)] found an identical de novo single-base substitution, a C-to-T change resulting in a silent gly-to-gly mutation at codon 608 (G608G) within exon 11 of the LMNA gene. This substitution created an exonic consensus splice donor sequence and resulted in activation of a cryptic splice site and deletion of 50 basepairs of prelamin A. This mutation was not identified in any of the 16 parents available for testing.

Phenotypic Data

Remarks

Publications

Cao H, Hegele RA, LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet48(5):271-4 2003

PubMed ID: 12768443

Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS, Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature423(6937):293-8 2003

PubMed ID: 12714972