Prevention of Albinism in an Iranian non-consanguineous family with pseudo dominant inheritance

Oculocutaneous albinism type 1 is characterized by hypopigmentation of the skin and hair and the distinctive ocular changes found in all types of the albinism, including: nystagmus; reduced iris pigment with iris translucency; reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination; foveal hypoplasia with substantial reduction in visual acuity; and misrouting of the optic nerve fiber radiations at the chiasm, resulting in strabismus. OCA1 is inherited in autosomal recessive manner. This study was designed to find the genetic defect in a 30 years-old affected female, having non-consanguineous parents, who was married with an apparently normal non-consanguineous male, and they wanted to know about recurrence of this disorder in their children. Sanger Sequencing of the TYR gene was performed for the affected individual. She was homozygote for a pathogenic variant in TYR gene (c.996G> A, p.M332I), and her parents were determined heterozygote for that mutation. Sanger Sequencing of the TYR gene was also performed for her husband. Accidently, he was heterozygote for another mutation in TYR gene (p. Arg402Gln). According to his wife, there is 50% possibility of inferring compound heterozygosity to each fetus. This 50% risk, resembles a pseudo-dominant inheritance in their children. Knowing these two mutations, they can use preimplantation genetic diagnosis (PGD) to assure that the embryos implanted are not affected, or use prenatal diagnosis. Genetic counseling and carrier detection is also recommended for all high-risk individuals in this family.

Keywords:

Oculocutaneous albinism , pseudo dominant inheritance , TYR gene , Sanger sequencing , PGD , Iran