A homozygous p.Glu150Lys mutation in the opsin gene of two Pakistani families with autosomal recessive retinitis pigmentosa.
OBJECTIVE
To identify the gene mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in Pakistani families.


METHODS
A cohort of consanguineous families with typical RP phenotype in patients was screened by homozygosity mapping using microsatellite markers that mapped close to 21 known arRP genes and five arRP loci. Mutation analysis was performed by direct sequencing of the candidate gene.


RESULTS
In two families, RP21 and RP53, homozygosity mapping suggested RHO, the gene encoding rhodopsin, as a candidate disease gene on chromosome 3q21. In six out of seven affected members from the two families, direct sequencing of RHO identified a homozygous c.448G>A mutation resulting in the p.Glu150Lys amino acid change. This variant was first reported in PMK197, an Indian arRP family. Single nucleotide polymorphism analysis in RP21, RP53, and PMK197 showed a common disease-associated haplotype in the three families.


CONCLUSIONS
In two consanguineous Pakistani families with typical arRP phenotype in the patients, we identified a disease-causing mutation (p.Glu150Lys) in the RHO gene. Single nucleotide polymorphism analysis suggests that the previously reported Indian family (PMK197) and the two Pakistani families studied here share the RHO p.Glu150Lys mutation due to a common ancestry.
Azam
Maleeha
M
Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
Khan
Muhammad Imran
MI
Gal
Andreas
A
Hussain
Alamdar
A
Shah
Syed Tahir Abbas
ST
Khan
Muhammad Shakil
MS
Sadeque
Ahmed
A
Bokhari
Habib
H
Collin
Rob W J
RW
Orth
Ulrike
U
van Genderen
Maria M
MM
den Hollander
A I
AI
Cremers
Frans P M
FP
Qamar
Raheel
R
D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016009:Chi-Square Distribution; D005190:Family; D005260:Female; D005654:Fundus Oculi; D005808:Genes, Recessive; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics*; D017421:Sequence Analysis
D012243:Rhodopsin