title: Comprehensive analysis of the molecular basis of oculocutaneous albinism in Indian patients lacking a mutation in the tyrosinase gene.
abstract: BACKGROUND
  Oculocutaneous albinism (OCA) refers to a group of inherited disorders where the patients have little or no pigment in the eyes, skin and hair. Mutations in genes regulating multi-step melanin biosynthesis are the basis of four 'classical' OCA types with overlapping clinical features. There are a few reports on defects in TYR and a single report on SLC45A2 in Indians affected with OCA but no report on OCA2 (a major locus related to the disease) and TYRP1.
  
  
  OBJECTIVE
  To assess and describe a comprehensive picture of the molecular genetic basis of OCA among Indians with no apparent mutations in TYR.
  
  
  METHODS
  Twenty-four affected pedigrees from 14 different ethnicities were analysed for mutations in OCA2, TYRP1, SLC45A2 and SLC24A5 using the polymerase chain reaction-sequencing approach.
  
  
  RESULTS
  Two splice-site and four missense mutations were detected in OCA2 in seven unrelated pedigrees, including four novel mutations. Haplotype analysis revealed a founder mutation (Ala787Thr) in two unrelated families of the same ethnicity. A patient homozygous for a novel SLC45A2 mutation also harboured a novel OCA2 defect. No mutation was detected in TYRP1 or SLC24A5.
  
  
  CONCLUSIONS
  Our results suggest that an OCA2 gene defect is the second most prevalent type of OCA in India after TYR. The presence of homozygous mutations in the affected pedigrees underscores the lack of intermixing between the affected ethnicities. Direct detection of the genetic lesions prevalent in specific ethnic groups could be used for carrier detection and genetic counselling to contain the disease.
authors.affiliation: Division of Molecular and Human Genetics, Indian Institute of Chemical Biology (a CSIR unit), 4 Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: M
authors.initials: M
authors.lastname: Sengupta
authors.forename: M
authors.initials: M
authors.lastname: Mondal
authors.forename: P
authors.initials: P
authors.lastname: Jaiswal
authors.forename: S
authors.initials: S
authors.lastname: Sinha
authors.forename: M
authors.initials: M
authors.lastname: Chaki
authors.forename: S
authors.initials: S
authors.lastname: Samanta
authors.forename: K
authors.initials: K
authors.lastname: Ray
mesh_terms: D016115:Albinism, Oculocutaneous / Q000208:ethnology / Q000235:genetics*; D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics; D017920:Antiporters / Q000235:genetics; D044466:Asian People; D004252:DNA Mutational Analysis; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000951:Antigens, Neoplasm; D017920:Antiporters; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C506584:SLC24A5 protein, human; C510061:SLC45A2 protein, human; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase