Prenatal diagnosis and carrier detection of albinism

Abstract

Oculocutaneus Albinism Type I (OCA I) comprises several phenotypes of hypopigmentation and low vision, caused by lack of tyrosinase activity, which results from homozygosity or compound heterozygosity of the defective autosomal recessive tyrosinase gene (TYR). Because of the severe visual handicap, affected families seek genetic counseling and prenatal diagnosis. Prenatal diagnosis of OCA I can be achieved by light and electron microscopic examination of melanogenesis in fetal scalp biopsies or by molecular genetic tests. The identification of the two mutated copies of TYR is achieved either by direct screening for mutations or by a combination of mutation detection and haplotype analysis, following the identification of only one mutation.We describe our experience in prenatal diagnosis of OCA I in families, with absolute and relative indications, using the histologic and molecular strategies. During the last ten years we performed 36 tests and diagnosed 7 albino and 29 normal fetuses. The diagnoses were confirmed in the newborns and in the aborted fetuses. 31 prenatal tests were done by fetal scalp biopsies using the histological approach. During the last 16 months we have performed 5 molecular genetic tests on DNA extracted from CVS or amniocytes, based on our population screen.We screened by molecular analyses 115 unrelated Israeli albinos and their families. In certain ethnic groups we found at least one mutation in all, and two mutations in over 90% of albinos. In these groups we offer mutation detection to normally pigmented unrelated spouses of albinos and of diagnosed carriers pertaining to OCA I families. Based on our findings, prenatal molecular diagnosis of OCA I becomes possible in an increasing number of Israeli albino families.