GM08369

GM08369 LCL from B-Lymphocyte

Description:

HEMOPHILIA B; HEMB
5,10-@METHYLENETETRAHYDROFOLATE REDUCTASE; MTHFR

Affected:

Yes

Sex:

Male

Age:

17 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Chromosome Abnormalities

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

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Factor IX deficiency diagnosed at age 15 mos; Factor IX level <1%; hemarthroses involving multiple joints & a massive intramuscular hematoma; prolonged PPT; mother & 2 sisters have normal Factor IX levels; donor subject is heterozygous for a C>T mutation at nucleotide 677 in exon 4 of the methylenetetrahydrofolate reductase (MTHFR) gene [677C>T] that results in a substitution of a valine for an alanine at codon 222 [Ala222Val (A222V)]; donor subject is homozygous normal for the R506Q mutation in the F5 gene and for the 20210G>A variant in the prothrombin gene (F2)

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

MTHFR

Chromosomal Location

1p36.3

Allelic Variant 1

607093.0003; MTHFR THERMOLABILE POLYMORPHISM

Identified Mutation

677C>T; Frosst et al. [Nature Genet. 10: 111-113 (1995)] identified a C-to-T substitution at nucleotide 677 that converted an alanine to a valine residue. The alteration created a HinfI site that was used to screen 114 unselected French-Canadian chromosomes; the allele frequency of the substitution was 0.38. The mutation in the heterozygous or homozygous state correlated with reduced enzyme activity and increased thermolability in lymphocyte extracts; in vitro expression of the mutagenized cDNA containing the mutation confirmed its effect on thermolability of MTHFR. Individuals homozygous for the mutation had significantly elevated plasma homocysteine levels. Thus, the 677C-T mutation may represent an important genetic risk factor in vascular disease.