GM04396

GM04396 LCL from B-Lymphocyte

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:

Male

Age:

6 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Nucleotide and Nucleic Acid Metabolism

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

Phenotypically normal; erythrocyte ADA deficiency diagnosed as part of a newborn screening program; transient diaper rash and oral thrush in first months of life; in first 2 years of life had a few colds and several episodes of otitis media; normal development with height and weight at 90th percentile; total lymphocyte counts were normal with 70% T cells on repeated determinations; delayed hypersensitivity to Candida albicans and mumps was present; responses of peripheral lymphocytes to PHA and allogeneic cells were normal; immunoglobulin levels rose appropriately with age; radiographs of chest, skull, and pelvis were normal; ADA activity in erythrocytes is undetectable; ADA enzyme activity in peripheral lymphocytes is 0.9% of control values with an immunoreactive ADA protein present at 1.6% of normal CRM; ADA activity and immunoreactive protein in lymphoblast culture detectable at 4% of control; ADA activity in fibroblasts detectable at 14% of control; dATP in RBC's is elevated; parents and brother have heterozygous levels of ADA activity; donor subject is a compound heterozygote: one allele has a T>C transition at nucleotide 320 in exon 4 of the ADA gene [320T>C] resulting in a substitution of proline for leucine at codon 107 [Leu107Pro (L107P)] and a second allele has a C>T transition at nucleotide 631 of the ADA gene [631C>T] resulting in a substitution of cysteine for arginine at codon 211 [Arg211Cys (R211C)]; same donor as GM04395 fibroblast.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

adenosine deaminase

Hirschhorn et al (J Clin Invest 71:1887-1892 1983) reported that the ADA activity in this cell culture was 5% of normal activity and had only a somewhat diminished heat stability. The enzyme showed a more anodal electrophoretic mobility than normal and had a lower more acidic isoelectric point (4.8 vs 4.9). As determined by HPLC there was no detectable difference in the molecular weight of the enzyme in this culture versus the ADA in normal cultures No abnormality in Km could be detected using adenosine as the substrate. EC Number: 3.5.4.4; 5% activity.

adenosine deaminase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.5.4.4; 14% activity.

adenosine deaminase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.5.4.4; 4% activity.

adenosine deaminase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.5.4.4; 0% activity.

Gene

ADA

Chromosomal Location

20q13.11

Allelic Variant 1

608958.0013; SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY

Identified Mutation

LEU107PRO; In GM07103 and GM04396, both cell lines from compound heterozygous patients, Hirschhorn et al. [Proc Natl Acad Sci U S A 87: 6171 (1990)] found a substitution of proline for leucine at amino acid 107 resulting from a T-to-C transition in nucleotide 320 in exon 4.

Gene

ADA

Chromosomal Location

20q13.11

Allelic Variant 2

608958.0014; ADA DEFICIENCY, PARTIAL

Identified Mutation

ARG211CYS; In cell line GM04396, from a compound heterozygous patient, Hirschhorn et al. [Proc Natl Acad Sci U S A 87: 6171 (1990)] found substitution of cysteine for arginine at amino acid 211 resulting from a C-to-T transition of nucleotide 631.

Phenotypic Data

Remarks

Publications

Hirschhorn R, Tzall S, Ellenbogen A, Hot spot mutations in adenosine deaminase deficiency. Proc Natl Acad Sci U S A87:6171-5 1990

PubMed ID: 2166947

Tzall S, Ellenbogen A, Eng F, Hirschhorn R, Identification and characterization of nine RFLPs at the adenosine deaminase (ADA) locus. Am J Hum Genet44:864-75 1989

PubMed ID: 2567118

Hirschhorn R, Ellenbogen A, Genetic heterogeneity in adenosine deaminase (ADA) deficiency: five different mutations in five new patients with partial ADA deficiency. Am J Hum Genet38:13-25 1986

PubMed ID: 3946419

Daddona PE, Mitchell BS, Meuwissen HJ, Davidson BL, Wilson JM, Koller CA, Adenosine deaminase deficiency with normal immune function. An acidic enzyme mutation. J Clin Invest72:483-92 1983

PubMed ID: 6603477

Hirschhorn R, Martiniuk F, Roegner-Maniscalco V, Ellenbogen A, Perignon JL, Jenkins T, Genetic heterogeneity in partial adenosine deaminase deficiency. J Clin Invest71:1887-92 1983

PubMed ID: 6863546