GM14641

GM14641 LCL from B-Lymphocyte

Description:

HEMOCHROMATOSIS; HFE
FACTOR V DEFICIENCY

Affected:

No

Sex:

Female

Age:

47 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Metal Metabolism

Alternate IDs

GM18064 [HEMOCHROMATOSIS; HFE]

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

mother

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically normal; affected son is GM14640 and affected spouse is GM14646; serum ferritin 31 ng/ml; serum iron 123 mcg/dl; donor subject is a compound heterozygote: allele one carries a G>A transition at nucleotide 845 in exon 4 of the HFE (HLA-H) gene [845G>A] resulting in a substitution of a tyrosine for a cysteine at codon 282 [Cys282Tyr (C282Y)]; allele two carries a C>G transversion at nucleotide 187 in exon 2 of the HFE (HLA-H) gene [187C>G] resulting in a substitution of aspartic acid for histidine at codon 63 [His63Asp (H63D)]; heterozygous for a G>A transition at nucleotide 1691 (1691G>A) of the Factor V (F5) gene resulting in a substitution of glutamine for arginine at codon 506 [Arg506Gln (R506Q)]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

MUTATION VERIFICATION

The Factor V Leiden mutation in this cell line has been verified by 5 laboratories. Methods used for mutation identification include: allele-specific amplification assay with gel electrophoresis; PCR + restriction endonuclease digestion and gel electrophoresis; Invader assay.

Gene

HFE

Chromosomal Location

6p22.2

Allelic Variant 1

613609.0001; HEMOCHROMATOSIS

Identified Mutation

CYS282TYR; A missense mutation caused by a G-to-A transition at nucleotide position 845 results in a cysteine to tyrosine transition at codon position 282 [cys282tyr (C282Y)] in the HFE gene.

Gene

Chromosomal Location

1q23

Allelic Variant 1

227400.0001; THROMBOPHILIA DUE TO DEFICIENCY OF COFACTOR FOR ACTIVATED PROTEIN

Identified Mutation

20009404T>C; Bertina et al. [Nature 369: 64-67 (1994)] identified a mutation in the F5 gene as the basis of deficiency of the cofactor of activated protein C in a family with APC resistance and proneness to thrombosis. In 2 patients classified as homozygous for the deficiency of the cofactor, they found homozygosity for a guanine-to-adenine substitution at nucleotide 1691. This mutation predicted the replacement of arg506 (CGA) by gln (CAA). They referred to the mutation as FV Q506 or FV Leiden. (This mutation is also known as R506Q, using the single letter symbols for the amino acid change. It is also known as G1691A, or, to avoid confusion of the single letter symbol for nucleotides with similar symbols for amino acids, 1691G-A.)

Gene

HFE

Chromosomal Location

6p22.2

Allelic Variant 2

613609.0002; HEMOCHROMATOSIS

Identified Mutation

HIS63ASP; A mutation caused by a C-to-G transversion in exon 2 results in a histidine to aspartic acid substitution at codon position 63 [his63asp (H63D)] in the HFE gene.

Phenotypic Data

Remarks

Publications

Bernacki SH, Beck JC, Muralidharan K, Schaefer FV, Shrimpton AE, Richie KL, Levin BC, Pont-Kingdon G, Stenzel TT., Characterization of publicly available lymphoblastoid cell lines for disease-associated mutations in 11 genes. Clin Chem51(11):2156-9 2005

PubMed ID: 16244288

Moser MJ, Marshall DJ, Grenier JK, Kieffer CD, Killeen AA, Ptacin JL, Richmond CS, Roesch EB, Scherrer CW, Sherrill CB, Van Hout CV, Zanton SJ, Prudent JR, Exploiting the enzymatic recognition of an unnatural base pair to develop a universal genetic analysis system. Clin Chem49(3):407-14 2003

PubMed ID: 12600952

Medintz I,Wong WW,Sensabaugh G,Mathies R, High speed single nucleotide polymorphism typing of a hereditary haemochromatosis mutation with capillary array electrophoresis microplates [In Process Citation] Electrophoresis21:2352-8 2000

PubMed ID: 10939445