Purchase this article with an account.
Claudia Yahalom, Dror Sharon, Efrat Shemesh, Shiran Ben Simhon, Dalia Eli, Anat Blumenfeld; The Segregation Of Two Inherited Ocular Conditions, Albinism And Aniridia, In Members Of A Single Family. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1561.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To describe the clinical manifestation and genetic analysis of a family in which siblings with mutations in the PAX6 and TYR genes were identified.
A couple who was interested in premarital genetic counselling was referred to our multidisciplinary low vision clinic. Both of them were legally blind: the female was considered as affected by albinism and the male - by Peter's anomaly. Genetic investigation revealed additional affected family members in both families. Eye examination including refraction, slit lamp and fundus examwas performed, as well as molecular genetic analysis by direct sequencing of PCR products and restriction digest for identification of specific mutations.
Upon clinical examination, typical diagnostic signs of albinism were seen in the female patient. Interestingly, she had very subtle clinical signs indicating a second severe eye disease. She had normal iris tissue, but the pupil was slightly decentred. Her cornea had a thin, peripheral pannus. Therefore, she was suspected to suffer from two different genetic conditions, namely aniridia and albinism. An extended eye examination of the female's family revealed the following: a brother with both signs of albinism and subtle aniridia, a sister and the mother with subtle aniridia signs (both were without diagnosis up to then), and the father with albinism type OCAIA. The clinical manifestations of aniridia were minimal in all affected family members, explaining why diagnosis was not reached till then. Screening of the coding region of the PAX6 gene revealed a novel heterozygous deletion of 9bp (c.233_241del9bp; p.V78_P80delinsA) confirming the suspected clinical diagnosis of aniridia. Oculocutaneous albinism type I was genetically confirmed: The albino father is homozygote for a severe TYR mutation p.G47D, the mother (not affected by albinism) carries the mutation p.M1V, both siblings affected by albinism are compound heterozygotes for p.G47D and p.M1V. In the male partner affected by Peter's anomaly, sequencing of the entire PAX6 gene, including exon-intron boundaries and intron sequences adjacent to the exons revealed no mutation. He is also not a carrier of a TYR gene mutation.
The co-existence of two severe autosomal genetic eye diseases, one recessive and one dominant, is rare but possible. A mild phenotype of aniridia can sometimes be difficult to diagnose, but proper clinical diagnosis is crucial for genetic counselling and family planning, as it was in this specific couple. A multidisciplinary team dealing daily with severe diseases causing blindness is a necessary set-up for such complicated cases.
This PDF is available to Subscribers Only