GM17547

GM17547 LCL from B-Lymphocyte

Description:

BRUTON AGAMMAGLOBULINEMIA TYROSINE KINASE; BTK

Affected:

Yes

Sex:

Male

Age:

14 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

X Chromosome Markers

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

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; at age 4 patient had recurrent pyogenic infections; IgG<50mg/dl; IgM<30mg/dl; IgA<20mg/dl; B lymphocytes express IgD and IgM; the cells synthesize small amounts of intracellular IgD, but there is no evidence of secretion; maternal uncle also has agammaglobulinemia; mother is GM17566; donor subject has T-to-C transition at nucleotide 1648 in exon 15 of the BTK gene (1648T>C) resulting in a substitution of arginine for cysteine at codon 506 in the middle of the kinase domain [Cys506Arg (C506R)]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

BTK

Chromosomal Location

Xq22.1

Allelic Variant 1

300300.0035; AGAMMAGLOBULINEMIA

Identified Mutation

CYS506ARG; In a patient with X-linked agammaglobulinemia, Hagemann et al. (1994) identified a T-to-C transition at position 1648 in exon 15, resulting in a substitution of arginine for cysteine-506 in the middle of the kinase domain. Whether this residue is directly involved in catalytic activity or substrate recognition is not clear.

Phenotypic Data

Remarks

Publications

Tao L, Boyd M, Gonye G, Malone B, Schwaber J, BTK mutations in patients with X-linked agammaglobulinemia: lack of correlation between presence of peripheral B lymphocytes and specific mutations. Hum Mutat16(6):528-9 2000

PubMed ID: 11102984

Schwaber J, Chen RH, Premature termination of variable gene rearrangement in B lymphocytes from X-linked agammaglobulinemia. J Clin Invest81(6):2004-9 1988

PubMed ID: 2838527

Schwaber J, Koenig N, Girard J, Correction of the molecular defect in B lymphocytes from X-linked agammaglobulinemia by cell fusion. J Clin Invest82(4):1471-6 1988

PubMed ID: 3139715

Schwaber J, Payne J, Chen R, B lymphocytes from X-linked agammaglobulinemia. Delayed expression of light chain and demonstration of Lyonization in carriers. J Clin Invest81(2):514-22 1988

PubMed ID: 3123521

Schwaber J, Lazarus H, Rosen FS, Restricted classes of immunoglobulin produced by a lymphoid cell line from a patient with agammaglobulinemia. Proc Natl Acad Sci U S A75(5):2421-3 1978

PubMed ID: 209464

Schwaber JF, Rosen FS, Induction of human immunoglobulin synthesis and secretion in somatic cell hybrids of mouse myeloma and human B lymphocytes from patients with agammaglobulinemia. J Exp Med148(4):974-86 1978

PubMed ID: 100574