Abstract
Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin. In this study, mutations in the TYR gene of 30 unrelated Iranian OCA1 patients and 100 healthy individuals were examined using PCR-sequencing. Additionally, in order to predict the possible effects of new mutations on the structure and function of tyrosinase, these mutations were analyzed by SIFT, PolyPhen and I-Mutant 2 software. Here, two new pathogenic p.C89S and p.H180R mutations were detected in two OCA1 patients. Moreover, the R402Q and S192Y variants, which are common non-pathogenic polymorphisms, were detected in 17.5% and 35% of the patients, respectively. The outcome of this study has extended the genotypic spectrum of OCA1 patients, which paves the way for more efficient carrier detection and genetic counseling.
Highlights
Oculocutaneous albinism (OCA) is a group of congenital heterogeneous disorders characterized by either complete or partial absence of pigment in the skin, hair and eyes because of the absence of or a defect in an enzyme involved in the production of melanin [1]
The prevalence of different forms of OCA fluctuates widely in different populations [4], where Oculocutaneous Albinism Type 1 (OCA1) is the most common subtype found in Caucasians and accounts for about 50% of all cases worldwide [5,6], while OCA2 is most common in Africa and accounts for about 30% of all cases worldwide [7]
OCA1 is caused by a mutation causing a complete lack of tyrosinase activity, while mutations resulting in the retainment of some enzyme activity result in OCA1B, where some melanin pigments are accumulated over time [8]
Summary
Oculocutaneous albinism (OCA) is a group of congenital heterogeneous disorders characterized by either complete or partial absence of pigment in the skin, hair and eyes because of the absence of or a defect in an enzyme involved in the production of melanin [1]. OCA type 1 (OCA1, MIM 203100) is the most severe form of albinism and is caused by mutations in the tyrosinase gene (TYR, MIM 606933; 11q14–q21). OCA1 is caused by a mutation causing a complete lack of tyrosinase activity, while mutations resulting in the retainment of some enzyme activity result in OCA1B, where some melanin pigments are accumulated over time [8]. Mutations in TYR can cause complete or partial OCA depending on residual activity [10]. Chromosome 11 contains a pseudogene known as Tyrosinase-Like Gene (TYRL, 11p11.2; MIM#191270). This gene shares 98.55% sequence identity with the 39–region of the TYR gene, including exons 4 and 5 [11]. The TYR gene was examined in individuals who met the clinical criteria proposed for OCA1, in order to characterize the associated mutations
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