GM09587

GM09587 LCL from B-Lymphocyte

Description:

ATAXIA-TELANGIECTASIA; AT
ATAXIA-TELANGIECTASIA MUTATED GENE; ATM

Affected:

Yes

Sex:

Male

Age:

39 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities

Class

Repair Defective and Chromosomal Instability Syndromes

Class

Syndromes with Increased Chromosome Breakage

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Similarly affected brother; onset at age 3; positive for telangiectasia; wheelchair at age 20; elevated alpha fetoprotein at age 39; no excess respiratory infections; compound heterozygote; the maternal allele carries a 4bp deletion at IVS59+1 which results in skipping of exon 59 leading to the deletion of 50 amino acids beginning at codon 2758 and the paternal allele carries a C>T mutation at nucleotide 9022 in exon 65 resulting in an amino acid change of R>C at codon 3008; in addition, the paternal allele carries a neutral sequence variation (735C>T) resulting in no change of the valine at codon 245

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227.

Gene

ATM

Chromosomal Location

11q22.3

Allelic Variant 1

skipped exon 59; ATAXIA-TELANGIECTASIA

Identified Mutation

IVS59+1del4

Gene

ATM

Chromosomal Location

11q22.3

Allelic Variant 2

ARG3008CYS; ATAXIA-TELANGIECTASIA

Identified Mutation

9022C>T

Phenotypic Data

Remarks

Publications

Hacia JG, Sun B, Hunt N, Edgemon K, Mosbrook D, Robbins C, Fodor SP, Tagle DA, Collins FS, Strategies for mutational analysis of the large multiexon ATM gene using high-density oligonucleotide arrays. Genome Res8(12):1245-58 1998

PubMed ID: 9872980

Concannon P, Gatti RA, Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia. Hum Mutat10(2):100-7 1997

PubMed ID: 9259193

Wei S, Charmley P, Concannon P, Organization, polymorphism, and expression of the human T-cell receptor AV1 subfamily. Immunogenetics45(6):405-12 1997

PubMed ID: 9089098

Gilad S, Khosravi R, Shkedy D, Uziel T, Ziv Y, Savitsky K, Rotman G, Smith S, Chessa L, Jorgensen TJ, Harnik R, Frydman M, Sanal O, Portnoi S, Goldwicz Z, Jaspers NG, Gatti RA, Lenoir G, Lavin MF, Tatsumi K, Wegner RD, Shiloh Y, Bar-Shira A, Predominance of null mutations in ataxia-telangiectasia. Hum Mol Genet5(4):433-9 1996

PubMed ID: 8845835

Wright J, Teraoka S, Onengut S, Tolun A, Gatti RA, Ochs HD, Concannon P, A high frequency of distinct ATM gene mutations in ataxia- telangiectasia. Am J Hum Genet59:839-46 1996

PubMed ID: 8808599