PURPOSE: Oculocutaneous albinism (OCA) is an autosomal recessive disorder of 
melanin biosynthesis that results in congenital hypopigmentation of ocular and 
cutaneous tissues. It is also associated with common developmental abnormalities 
of the eye. Mutations in the solute carrier family 45, member 2 gene (SLC45A2, 
also called MATP) cause oculocutaneous albinism type 4 (OCA4), which is the 
second most prevalent type of OCA in Japan. So far, 24 pathological mutations 
have been reported in SLC45A2, but there is no report from India. Interestingly, 
in almost 31% of the cases, the second mutation has never been found. The 
purpose of this study was to investigate the molecular basis of OCA among 
Indians using SLC45A2 as the candidate gene.
METHODS: From our patient pool, consisting of 50 unrelated OCA pedigrees 
covering 17 ethnic groups of eastern and southern India, 20 patients (from 19 
affected families) lacking any mutation in the tyrosinase gene (TYR) were 
screened further for nucleotide variants in SLC45A2. All seven exons and 
splice-site junctions of SLC45A2 were amplified and sequenced from the OCA 
patients and from 50 ethnically matched healthy controls. Nucleotide changes 
were detected by identifying 'double peaks' in the chromatogram due to 
heterozygosity as well as by pairwise BLAST analysis of the sequence output data 
with a normal copy of SLC45A2. Haplotype analysis was done among the affected 
sibs using three newly identified microsatellite markers placed within and in 
flanking regions of the SLC45A2 locus.
RESULTS: Four novel mutations (c.126G>A [Met42Ile], c.190G>A [Gly64Ser], 
c.904A>T [Thr302Ser], and c.1042C>T [Arg348Cys]) and one reported mutation 
(c.469G>A [Asp157Asn]) were identified in SLC45A2. All the novel changes 
cosegregated with the disease and none were present in control samples. 
Consistent with previous reports, we did not find the second mutant allele in 
three unrelated patients. Haplotype analysis using microsatellite markers in the 
family of one such proband suggested that the affected sibs inherited the mutant 
allele (Arg348Cys) from their father but different SLC45A2 alleles from the 
mother. In addition, five single nucleotide variants were identified which 
included E272K and L374F polymorphisms that have been reported to be associated 
with human ethnicities.
CONCLUSIONS: Our study reveals that 10% of the total OCA cases from eastern and 
southern Indian ethnic groups carry mutations in SLC45A2. Among 10 variants 
found in the gene, five are pathogenic changes. Our data, based on haplotype 
analysis on a single family, suggest that the disease is caused in the affected 
sibs either by a single mutation in SLC45A2 and a defect in another locus, or 
SLC45A2 is not responsible for the disorder in the family, but the pathogenesis 
is caused by a mutation in another gene not yet characterized in these patients.