AG19912

AG19912 LCL from B-Lymphocyte

Description:

WERNER SYNDROME; WRN REPLICATION FOCUS-FORMING ACTIVITY 1, INCLUDED; FFA1, INCLUDED
LAMIN A/C; LMNA

Affected:

Yes

Sex:

Female

Age:

19 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

Black/African American

Ethnicity

AFRICAN-AMERICAN

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

ISCN

46,XX

Species

Homo sapiens

Common Name

Human

Remarks

Atypical; clinically affected; African-American; atypical; affected father, paternal aunt, paternal grandmother and paternal great aunt; cannot stay on feet long; hips and knees hurt; restricted movement in wrists and ankles; double jointed knees; insulin-resistant diabetes mellitus; appearance of premature aging; short stature; height 155 cm; thin limbs; pinched, bird-like facial features; some gray in hair; thinning hair; peripheral loss of subcutaneous fat; very dry atrophic skin; hypermelanosis; cold fingers; the karyotype is 46,XX. This donor is heterozygous for a G-to-T substitution at nucleotide 813 (813G>T) in exon 2 of the LMNA gene, resulting in a missense mutation in codon 133 [ARG133LEU (R133L)]. The legacy karyotype description shown in this Remark may not be representative of the current available product.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

LMNA

Chromosomal Location

1q21.2

Allelic Variant 1

150330.0027; WERNER SYNDROME, ATYPICAL

Identified Mutation

ARG133LEU; In 2 unrelated persons in whom a diagnosis of Werner syndrome (277700) had been made but no mutation found in the Werner syndrome gene (RECQL2; 604611), Chen et al. (2003) found heterozygosity for the R1333L mutation in the LMNA gene. One was a white Portuguese female who presented at the age of 9 years with short stature. She showed scleroderma-like skin changes and graying/thinning of hair. Type 2 diabetes developed at the age of 23 years. Hypogonadism, osteoporosis, and voice changes were also present. The other patient was an African American female in whom the diagnosis of Werner syndrome was made at the age of 18 years. Scleroderma-like skin, short stature, graying/thinning of hair, and type 2 diabetes at the age of 18 years were features. The deceased father, paternal aunt, and paternal grandmother of this patient were also diagnosed with severe insulin-resistant diabetes mellitus, suggesting that the R133L mutation might have been paternally inherited.

Phenotypic Data

Remarks

Publications

Chen L, Lee L, Kudlow BA, Dos Santos HG, Sletvold O, Shafeghati Y, Botha EG, Garg A, Hanson NB, Martin GM, Mian IS, Kennedy BK, Oshima J, LMNA mutations in atypical Werner's syndrome. Lancet362(9382):440-5 2003

PubMed ID: 12927431