Molecular genetic analysis of retinitis pigmentosa in Indonesia using genome-wide homozygosity mapping
Publication year
2011Source
Molecular Vision, 17, (2011), pp. 3013-24ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Human Genetics
Ophthalmology
Journal title
Molecular Vision
Volume
vol. 17
Page start
p. 3013
Page end
p. 24
Subject
IGMD 3: Genomic disorders and inherited multi-system disorders; NCMLS 6: Genetics and epigenetic pathways of disease; NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disordersAbstract
PURPOSE: 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.
This item appears in the following Collection(s)
- Academic publications [203856]
- Electronic publications [102283]
- Faculty of Medical Sciences [80326]
- Open Access publications [70938]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.