AG07091

AG07091 LCL from B-Lymphocyte

Description:

MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY; MADA
LAMIN A/C; LMNA
NIA AGING CELL REPOSITORY DNA PANEL - AGING SYNDROMES

Affected:

Yes

Sex:

Female

Age:

28 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: short stature, alopecia, severe osteoporosis with resorption of clavicles and upper ribs, multiple fractures, typical facies, and dystrophic nails with resorption of distal phalanges. Unusual features are absence of coronary artery occlusions at age 28, and monthly menses since age 15. Parents and seven sibs are clinically unaffected. The blood specimen was obtained ante-mortem. The culture was initiated on 10/12/83 by transformation with Epstein-Barr virus. The culture grows in suspension, and the cell morphology is spherical. Donor subject is a compound heterozygote: one allele carries an Arg471 to Cys mutation [Arg471Cys (R471C)] in exon 8 of the Lamin A gene (LMNA) resulting from a 1623C>T transition; the second allele has a C>T transition at nucleotide 1791 (1791C>T) resulting in an Arg-to-Cys substitution at codon 527 in exon 9 [Arg527Cys (R527C)].

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

LMNA

Chromosomal Location

1q21.2

Allelic Variant 1

150330.0025; MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY

Identified Mutation

ARG471CYS; Description: In a patient who was thought to have a typical progeria phenotype (176670) and was 28 years old at the time that DNA was obtained, Cao and Hegele [J. Hum. Genet. 48: 271-274 (2003)] identified compound heterozygosity for 2 missense mutations in the LMNA gene. One mutation, arg471 to cys (R471C), resulted from a 1623C>T transition. An arg527cys (R527C) substitution (150330.0026), resulting from a 1791C>T transition, was found on the other allele. These mutations were not identified in any of 100 control chromosomes.

Gene

LMNA

Chromosomal Location

1q21.2

Allelic Variant 2

150330.0026; MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY

Identified Mutation

ARG527CYS; Description: See 150330.0025, Cao and Hegele [J. Hum. Genet. 48: 271-274 (2003)] and Brown (2004).

Phenotypic Data

Remarks

Publications

Bracci AN, Dallmann A, Ding Q, Hubisz MJ, Caballero M, Koren A, The evolution of the human DNA replication timing program Proceedings of the National Academy of Sciences of the United States of America120:e2213896120 2023

PubMed ID: 36848554

Caballero M, Ge T, Rebelo AR, Seo S, Kim S, Brooks K, Zuccaro M, Kanagaraj R, Vershkov D, Kim D, Smogorzewska A, Smolka M, Benvenisty N, West SC, Egli D, Mace EM, Koren A, Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation Human molecular genetics120:e2213896120 2021

PubMed ID: 35394024

Narisu N, Rothwell R, Vrtacnik P, Rodríguez S, Didion J, Zöllner S, Erdos MR, Collins FS, Eriksson M, Analysis of somatic mutations identifies signs of selection during in vitro aging of primary dermal fibroblasts Aging cell120:e13010 2018

PubMed ID: 31385397

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