AG10801

AG10801 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:

Female

Age:

6 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

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, severe failure to thrive, mandibular hypoplasia, coxa valga, loss of subcutaneous tissue and flexion contractures of the fingers and toes. The blood specimen was taken ante-mortem on 1/25/90. Culture was initiated on 1/26/90 by transformation of lymphocytes with Epstein Barr virus. The cells grow in suspension and their morphology is spherical. Donor subject has a de novo single base substitution, a G>A change at nucleotide 2034 (2034G>A), which results in a change at codon 608 [Gly608Ser (G608S)] 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 150 bp of the LMNA mRNA leading to the deletion of 50 amino acids from the protein. This altered LMNA protein was detected by 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

150330.0023; HUTCHINSON-GILFORD PROGERIA SYNDROME

Identified Mutation

GLY608SER; Description: In a patient with Hutchinson-Gilford progeria syndrome (176670), Eriksson et al. [Nature 423: 293 (2003)] identified a G-to-A transition in the LMNA gene resulting in a gly-to-ser substitution at codon 608 (G608S). This mutation was not identified in either parent.

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