The biochemical analysis of OA1 mutations performed in this study provides important insights into the structure-function relationships of the OA1 protein and implies protein misfolding as a major pathogenic mechanism in OA1.
The findings of the present study expanded the gene mutation spectrum of GPR143 and investigated the clinical phenotype of patients with OA1 in the Chinese population.
These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.
These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.
All nine exons of the OA1 gene, as well as the 5' and 3' untranslated regions, were scanned for point mutations in PCR-amplified DNA from 60 OA1 patients.
In this study, we screened the human Gαi3 gene, GNAI3, in DNA samples from 26 patients who had all clinical characteristics of OA but in whom a specific mutation in the OA1 gene had not been found, and in 6 normal control individuals.
Mutation analysis of the OA1 gene demonstrated seven presumed pathogenic mutations in the nine families with XLOA: five single nucleotide substitutions predicting a change of conserved amino acids (G35D, L39R, D78V, W133R and E233K) when compared with the mouse OA1 homologue, one deletion leading to the skipping of exon 2, and one single nucleotide substitution expected to affect the 5' splice site of intron 2 were found.
Our study performed mutation analysis of the G protein-coupled receptor 143 gene (GPR143) and assessed the clinical characteristics of OA1 in three Chinese families.
We screened 172 index patients with a clinical diagnosis of OA or OCA based on the classical findings, to evaluate the frequency of sequence variants in tyrosinase (TYR), P-gene, P-protein (OCA2), and the G-protein-coupled receptor 143 gene, OA1 (GPR143).
We present a hierarchical strategy for mutation screening for diagnostic testing for OA1 that comprises two tiers: first, multiplex PCR to detect intragenic deletions in the OA1 gene with denaturing high-performance liquid chromatography (dHPLC), and, second, heteroduplex analysis with dHPLC to scan for mutations, with subsequent sequencing of variants to confirm putative mutations in the OA1 gene.