X-linked ocular albinism: prevalence and mutations--a national study

In a national retrospective register study 112 patients with ocular albinism (OA) were identified, including 60 male patients with proven or presumed X-linked ocular albinism (XLOA). Based on the birth year cohorts 1960-1989, an XLOA point prevalence at birth of 1 in 60,000 live-born was calculated. We identified 14 XLOA families in the Danish population, and obtained DNA from affected persons in nine families. 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. Subsequent genealogical investigations in the three families harbouring the same mutation disclosed that two of the three pedigrees belonged to the same family. All mutations predict crucial changes in the protein structure. Clinical examination failed to identify any phenotype-genotype pattern except a milder phenotype devoid of iris translucency in the patient with the 5'splice site mutation of intron 2.