GM02213

GM02213 LCL from B-Lymphocyte

Description:

PORPHYRIA, ACUTE INTERMITTENT
HYDROXYMETHYLBILANE SYNTHASE; HMBS

Affected:

Yes

Sex:

Female

Age:

62 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Other Disorders of Known Biochemistry

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

Deficient uroporphyrinogen-I synthetase; active AIP; donor subject is heterozygous for a C>T transition at nucleotide 499 in exon 10 of the HMBS gene (499C>T) resulting in the substitution of tryptophan for arginine at codon 167 [Arg167Trp (R167W)]

Characterizations

hydroxymethylbilane synthase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 2.5.1.61

Gene

HMBS

Chromosomal Location

11q23.3

Allelic Variant 1

609806.0013; PORPHYRIA, ACUTE INTERMITTENT

Identified Mutation

ARG167TRP; In a brother and sister with severe AIP, Llewellyn et al. (1992) identified compound heterozygosity for adjacent base transitions in the PBGD gene. One of the mutations was the arg167-to-gln mutation (176000.0005) due to a G-to-A transition in nucleotide 500. The other mutation, not previously described, was a C-to-T transition in nucleotide 499 resulting in substitution of tryptophan for arginine. The seemingly high frequency of mutations in exon 10 (Delfau et al., 1990) prompted Gu et al. (1992) to screen this exon in 41 unrelated AIP patients by use of denaturing gradient gel electrophoresis (DGGE) after PCR amplification. In about one-fourth of the patients, they distinguished 3 abnormal migration patterns, indicating the presence of mutation in heterozygous state. Sequencing demonstrated the presence of 3 different single-base substitutions, 2 of which had already been described (Delfau et al., 1990). A third one consisted of a C-to-T transition located at position 499 of the PBGD mRNA which resulted in an arg-to-trp substitution at codon 167. All 3 mutations occurred in patients with crossreacting immunologic material, i.e., the CRIM-positive form of AIP. In Finland, Kauppinen et al. (1992) found the arg167-to-trp mutation in 3 out of 7 families with CRIM-positive AIP. All 3 had type 2 CRIM-positive AIP. DNA analyses of family members demonstrated that conventional assays of erythrocyte PBGD activity identified correctly only 72% of the carriers of the mutation.