title: Molecular genetic analysis of retinitis pigmentosa in Indonesia using genome-wide homozygosity mapping.
abstract: OBJECTIVE
  Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous retinal disorder. Despite tremendous knowledge about the genes involved in RP, little is known about the genetic causes of RP in Indonesia. Here, we aim to identify the molecular genetic causes underlying RP in a small cohort of Indonesian patients, using genome-wide homozygosity mapping.
  
  
  METHODS
  DNA samples from affected and healthy individuals from 14 Indonesian families segregating autosomal recessive, X-linked, or isolated RP were collected. Homozygosity mapping was conducted using Illumina 6k or Affymetrix 5.0 single nucleotide polymorphism (SNP) arrays. Known autosomal recessive RP (arRP) genes residing in homozygous regions and X-linked RP genes were sequenced for mutations.
  
  
  RESULTS
  In ten out of the 14 families, homozygous regions were identified that contained genes known to be involved in the pathogenesis of RP. Sequence analysis of these genes revealed seven novel homozygous mutations in ATP-binding cassette, sub-family A, member 4 (ABCA4), crumbs homolog 1 (CRB1), eyes shut homolog (Drosophila) (EYS), c-mer proto-oncogene tyrosine kinase (MERTK), nuclear receptor subfamily 2, group E, member 3 (NR2E3) and phosphodiesterase 6A, cGMP-specific, rod, alpha (PDE6A), all segregating in the respective families. No mutations were identified in the X-linked genes retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (X-linked recessive; RP2).
  
  
  CONCLUSIONS
  Homozygosity mapping is a powerful tool to identify the genetic defects underlying RP in the Indonesian population. Compared to studies involving patients from other populations, the same genes appear to be implicated in the etiology of recessive RP in Indonesia, although all mutations that were discovered are novel and as such may be unique for this population.
authors: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors: Anna M
authors: AM
authors: Siemiatkowska
authors: Kentar
authors: K
authors: Arimadyo
authors: Luminita M
authors: LM
authors: Moruz
authors: Galuh D N
authors: GD
authors: Astuti
authors: Marta
authors: M
authors: de Castro-Miro
authors: Marijke N
authors: MN
authors: Zonneveld
authors: Tim M
authors: TM
authors: Strom
authors: Ilse J
authors: IJ
authors: de Wijs
authors: Lies H
authors: LH
authors: Hoefsloot
authors: Sultana M H
authors: SM
authors: Faradz
authors: Frans P M
authors: FP
authors: Cremers
authors: Anneke I
authors: AI
authors: den Hollander
authors: Rob W J
authors: RW
authors: Collin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D050172:Genes, X-Linked; D005820:Genetic Testing; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D000090063:Proto-Oncogene Mas; D012174:Retinitis Pigmentosa / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: D005136:Eye Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas