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Anat Blumenfeld, Dalia Eli, Idit Bejarano-Achache, Efrat Shemesh, Irene Anteby, Claudia Yahalom, Ada Rosenmann; Prenatal Molecular Diagnosis of Oculocutaneous Albinism (OCA) in a Large Cohort of Israeli Families. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1358.
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© ARVO (1962-2015); The Authors (2016-present)
To present the prenatal molecular test results of OCA types 1, 2 and 4 caused by mutations in the tyrosinase (TYR), P and SLC45A2 genes, respectively, in a large cohort of Israeli albino families.
Clinical evaluation of subtypes of OCA included hair skin and eye examination. Detailed genetic investigation included pedigree analysis and ethnic origin of all 4 grandparents. Further genetic counseling was performed after the completion of molecular tests of the propositus and parents, prior to, and after each prenatal test. Following prenatal molecular test genetic counseling included prediction of the spectrum of expected phenotypes based on diagnosed genotypes. Molecular prenatal tests were performed on extracted DNA using the combination of PCR followed by direct mutation screen, direct sequencing, and haplotype analysis.
77 prenatal tests were performed in 48 families; in 35 - the propositus was the child and in 13 - a parent or a close relative. In 39 families TYR mutations were diagnosed, in 8 families P mutations, and in one family a SLC45A2 mutation was identified. 19 albino fetuses were diagnosed. Following further genetic counseling most couples elected to terminate the pregnancy. Three couples (4 pregnancies) elected not to terminate the pregnancy of an albino fetus due to expected variable phenotype of albinism. Several additional pregnancies were terminated for other reasons. In 4 families the propositus was a close relative of one parent and the other parent carried the R402Q change in TYR. In most individuals R402Q is a non-pathogenic polymorphism and compound heterozygotes (CH) are normally pigmented, but some CH have various degrees of albinism. One fetus was CH for R402Q / R402X and a normally pigmented child was born. One couple in which the father was a grandchild of an albino and carried a “severe” TYR mutation and the mother carried R402Q elected not to perform prenatal test and an albino girl CH for the “severe” TYR mutation and R402Q was born.
Families with increased risk for an albino child with severe visual handicap seek prenatal genetic counseling and testing for the prevention of affected offspring. Unless mild phenotype of albinism is predicted, couples elect to terminate the pregnancy of an albino fetus. Molecular genetic testing at our center enables a nationwide approach for the prevention of a severe phenotype of albinism.
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