Description:
PORPHYRIA, ACUTE INTERMITTENT
HYDROXYMETHYLBILANE SYNTHASE; HMBS
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
| Class |
Other Disorders of Known Biochemistry |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
|
Biopsy Source
|
Peripheral vein
|
|
Cell Type
|
B-Lymphocyte
|
|
Tissue Type
|
Blood
|
|
Transformant
|
Epstein-Barr Virus
|
|
Sample Source
|
DNA from LCL
|
|
Race
|
White
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| 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.
|
| 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)] |
|
|