Oculocutaneous albinism (OCA) is a hereditary disease of pigment absence in eyes, skin and hair due to the lack of congenital melanocyte.OCA is classified into 7 types based on different genetic mutations, and the mutation of tyrosinase (TYR) gene causes OCA type 1 (OCA1). OCA has obvious genetic heterogeneity and phenotypic heterogeneity.The molecular diagnosis of the mutant gene is helpful for the classification and molecular pathogenesis study of OCA.
This study was to screen the TYR mutation in OCA patients, and to analyze the association between the gene mutation type and clinical phenotype.
Ten patients with OCA were enrolled in Tianjin Ophthalmological Hospital from January 2011 to December 2014.The clinical and ocular manifestations of the patients were examined.Peripheral venous blood 3 ml was collected in the patients and their lineal relatives for the extraction of genomic DNA.Extracted DNA was amplified by PCR and the TYR gene sequence was analyzed, including all 5 exon coding sequence and exon 5’ and 3’ end and the non-coding region sequence of intron splicing in TYR gene.This study complied with Helsinki Declaration and the protocol was approved by Ethic Committee of Tianjin Eye Hospital.Informed consent was obtained from each subject.
All the patients showed white or reddish hair and snow-white skin, and different degrees of pigment lack was seen in iris.The best corrected visual acuity of the patients was 0.05-0.2, and 3 patients complicated with nystagmus.Fundus findings showed a sunset-like change and dysplasia of macula.The TYR gene sequencing revealed that patient 1 was OCA1A subtype, with the compound heterozygous mutant of c. 832C>T (p.R278X) and c. 1217C>T (p.P406L), and his/her parents occurred the heterozygous mutation of exons P406L and R278X.The phenotype of the patient 1 was white hair and white iris.The patient 3 was OCA1B subtype, with the compound heterozygous mutations of c. 1265G>A (p.R422Q) and c. 1217C>T ( p. P406L), showing an appearance of reddish brown hair and sallow iris.TYR gene mutant was not detected in other 8 patients.
The mutation of TYR gene is the main cause of OCA1 type.The phenotype of OCA1A subtype is no pigment in eyes and hair, and one of OCA1B subtype was obviously lessening of pigment.The difference of mutant genes of OCA is the cause of genetic and phenotypic heterogeneity.