Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. Six genes are associated with autosomal recessive OCA (TYR， OCA2， TYRP1， SLC45A2， SLC24A5 and LRMDA)， and one gene， GPR143， is associated with X-linked ocular albinism (OA). Molecular genetic analysis provides a genetic diagnosis in approximately 60% of individuals with clinical OA/OCA. A considerably number of the remaining 40% are heterozygous for a causative sequence variation in TYR. To identify missing causative sequence variants in these， we used a NGS based approach， genotyping and segregation analysis. We report two putative pathogenic haplotypes which only differ by two extremely rare SNVs， indicating that the ha... More
Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. Six genes are associated with autosomal recessive OCA (TYR， OCA2， TYRP1， SLC45A2， SLC24A5 and LRMDA)， and one gene， GPR143， is associated with X-linked ocular albinism (OA). Molecular genetic analysis provides a genetic diagnosis in approximately 60% of individuals with clinical OA/OCA. A considerably number of the remaining 40% are heterozygous for a causative sequence variation in TYR. To identify missing causative sequence variants in these， we used a NGS based approach， genotyping and segregation analysis. We report two putative pathogenic haplotypes which only differ by two extremely rare SNVs， indicating that the haplotypes have a common derivation. Both haplotypes segregate consistent with an autosomal recessive inheritance pattern and include the allele p.S192Y-p.R402Q. An explanation for the pathogenicity of the haplotypes could be the combination of p.S192Y and p.R402Q. Homozygosity for the pathogenic haplotypes causes a partial albinism phenotype. In our cohort， 15% of affected individuals had a molecular genetic diagnosis involving the pathogenic haplotype. Consequently， the prevalence of albinism seems to be substantially underestimated， and children with unexplained bilateral subnormal vision and/or nystagmus should be analysed clinically and molecularly for albinism.
