GM02824

GM02824 Fibroblast

Description:

SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY
ADENOSINE DEAMINASE; ADA

Affected:

Yes

Sex:

Female

Age:

4 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Nucleotide and Nucleic Acid Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; lymphoblastoid cell line contains less than 5% of normal ADA activity and immunoreactive protein; absent IgM and IgA; weak MLC response; absent T cells; no detectable ADA activity in erythrocytes; normal ADA mRNA level but cells contain mRNAs of abnormal size; normal ADA mRNAs and ADA mRNAs missing exon 4 are present in approximately equal abundance; donor subject is a compund heterozygote: one allele has a C>T transition at nucleotide 1081 in exon 11 of the ADA gene [1081C>T] resulting in a substitution of valine for alanine at codon 329 [Ala329Val(A329V)] and a second allele has an A>G transition in the 3-prime splice site of intron 3 of the ADA gene resulting in a deletion of exon 4 from mature RNA; same donor as GM02825 lymphocyte.

Characterizations

Passage Frozen

adenosine deaminase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.5.4.4; <5% activity.

Gene

ADA

Chromosomal Location

20q13.11

Allelic Variant 1

608958.0006; SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY

Identified Mutation

ALA329VAL; In GM02756, Akeson et al. [Proc Natl Acad Sci U S A 84: 5947 (1987)] demonstrated 2 different mutant alleles: one was ala329 to val; the other was a 632G-A transition in the ADA gene, resulting in the replacement of the arginine residue by histidine at codon 211 (102700.0004). In addition, Akeson et al. [Proc Natl Acad Sci U S A 84: 5947 (1987)] and [J Biol Chem 263:16291 (1988)] found that cell line GM02825A was a genetic compound. One allele had an ala329-to-val change (102700.0006); the other allele had a point mutation from A to G in the 3-prime splice site of intron 3 (102700.0017), resulting in elimination of exon 4 from the mature mRNA.

Gene

ADA

Chromosomal Location

20q13.11

Allelic Variant 2

608958.0017; SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY

Identified Mutation

IVS3AS, A>G, -2, EX4DEL; Akeson et al. [Proc Natl Acad Sci U S A 84: 5947 (1987)] and [J Biol Chem 263:16291 (1988)] found that cell line GM02825 was a genetic compound. One allele had an ala39-to-val change (102700.0006); the other allele had a point mutation from A to G in the 3-prime splice site of intron 3 (102700.0017), resulting in elimination of exon 4 from the mature mRNA.