DNA-based prenatal diagnosis of a Korean family with tyrosinase-related oculocutaneous albinism (OCA1)

Tyrosinase-related oculocutaneous albinism (OCA1), an autosomal recessive inborn error of pigmentation, is caused by the deficiency of tyrosinase. We had previously identified two different mutations of the TYR gene in a four year old Korean male with mild OCA; a P310insC frameshift in exon 2 and an IVS2-7t→a,-10 - 11deltt splice junction mutation in exon 3. Here we report a prenatal diagnostic study of a subsequent fetus of the above family that was at 25% risk of OCA1. SSCP/heteroduplex screening, restriction enzyme digestion, and allele-specific oligonucleotide hybridization analyses of DNA obtained by chorionic villus sampling indicated that the fetus was a compound heterozygote for the paternal P310insC and the maternal IVS2- 7t→a,-10--11deltt mutations. The diagnosis was later confirmed by observation of poorly pigmented irides of the abortus terminated at the 18th week of gestation. This approach provides a fast and reliable method for DNA- based prenatal diagnosis when specific mutations are known in families at high risk of OCA1.