Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1)

PLoS One. 2014 Sep 12;9(9):e106656. doi: 10.1371/journal.pone.0106656. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Albinism, Oculocutaneous / enzymology*
  • Albinism, Oculocutaneous / genetics*
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Databases, Genetic
  • Electrophoresis, Agar Gel
  • Exons / genetics
  • Female
  • Humans
  • Iran
  • Male
  • Molecular Sequence Data
  • Monophenol Monooxygenase / genetics*
  • Mutation / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Young Adult

Substances

  • Monophenol Monooxygenase

Supplementary concepts

  • Oculocutaneous albinism type 1

Grants and funding

The authors would like to thank all the participants for the blood donation from the Medical Genetics Department at the Special Medical Center, Tehran, Iran. The authors would like to express their utmost gratitude and appreciation to University of Malaya Research Grant (RG084-13BIO), IPPP grant (PG082-2013B), BKP grant (BK020-2012) and Malaysian Ministry of Higher Education's MOHE-HIR Grants (UM.C/625/1/MOHE/MED/17 and UM.C/625/1/MOHE/MED/33) for providing partial financial supports to conduct this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.