Identification of recurrent and novel mutations in TULP1 in Pakistani families with early-onset retinitis pigmentosa
Publication year
2012Source
Molecular Vision, 18, (2012), pp. 1226-1237ISSN
Publication type
Article / Letter to editor

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Organization
Human Genetics
Ophthalmology
CMBI
Journal title
Molecular Vision
Volume
vol. 18
Page start
p. 1226
Page end
p. 1237
Subject
NCMLS 6: Genetics and epigenetic pathways of disease; NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disorders; NCMLS 7: Chemical and physical biologyAbstract
PURPOSE: To identify the genetic defects underlying retinitis pigmentosa (RP) in Pakistani families. METHODS: Genome-wide high-density single-nucleotide-polymorphism microarray analysis was performed using the DNA of nine affected individuals from two large families with multiple consanguineous marriages. Data were analyzed to identify homozygous regions that are shared by affected sibs in each family. Sanger sequencing was performed for genes previously implicated in autosomal recessive RP and allied retinal dystrophies that resided in the identified homozygous regions. Probands from both families underwent fundus examination and electroretinogram measurements. RESULTS: The tubby-like protein 1 gene (TULP1) was present in the largest homozygous region in both families. Sequence analysis identified a previously reported mutation (c.1138A>G; p.Thr380Ala) in one family and a novel pathogenic variant (c.1445G>A; p.Arg482Gln) in the other family. Both variants were found to be present in a homozygous state in all affected individuals, were heterozygous present in the unaffected parents, and heterozygous present or absent in normal individuals. Affected individuals of both families showed an early-onset form of RP. CONCLUSIONS: Homozygosity mapping, combined with candidate-gene analysis, successfully identified genetic defects in TULP1 in two large Pakistani families with early-onset retinitis pigmentosa.
This item appears in the following Collection(s)
- Academic publications [202652]
- Electronic publications [100821]
- Faculty of Medical Sciences [79967]
- Open Access publications [69553]
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