Molecular Analysis Of Tyr, P, Tyrp1 And Gpr143 Genes In Italian Patients With Oculocutaneous And Ocular Albinism

Abstract

Purpose: : In this study 117 patients with oculocutaneous or ocular albinism have been characterized for TYR, P-protein, TYRP1 and GPR143 gene defects, associated to the different phenotypes OCA1, OCA2, OCA3 and OA1 in order to describe their variation frequencies in Italian population.

Methods: : After clinical examination and instrumental evaluation by our Ophthalmologic Centre, all affected patients received a genetic counseling and signed an informed consent to the genetic study. A blood sample was collected from each individual and , when possible, also from parents. After DNA extraction, different PCR amplifications and automatic sequences of TYR, P-protein, TYRP1 and GPR143 genes were performed. SeqScape software analysis was then applied to individuate DNA variations.

Results: : We analyzed all OCA patients for TYR gene and we identified 6 homozygous patients, 33 compound heterozygotes and 12 heterozygotes. P-gene was analyzed in 31 patients without TYR mutations and we identified 2 patients with the already described exon 7 deletion, one patient with a big deletion that include the region from exon 12 to exon 18 in homozygosis status, 5 compound heterozygotes and 5 patients with only one heterozygous mutation. Among the TYR and P-protein negative cases we analyzed 27 patients for TYRP1 gene and we identified one homozygous patient for a new mutation, one compound heterozygote and one patient with only one mutation in heterozygosis status. One patient presents a digenic heredity with one mutation in P-protein and the other in TYRP1 gene. The pathological variations we identified are missense and nonsense mutations, small deletions or duplications, splicing defects and gross deletions. We also analyzed 6 male patients with a probable OA1 phenotype and compatible X-linked segregation for GPR143 and we identified one patient with a complete deletion of exon 2.

Conclusions: : In our cohort of albinos patients quite 45% have mutations in TYR gene, associated to OCA1A and OCA1B phenotype, but also molecular defects have been found in OCA2 and OCA3 related genes, prevalent described in other different ethnic populations. For the first time a new digenic form is also identified.

Keywords: gene screening • iris • radiation damage: light/UV