Retinitis pigmentosa: mutation analysis of RHO, PRPF31, RP1, and IMPDH1 genes in patients from India.
OBJECTIVE
To screen for possible disease-causing mutations in rhodopsin (RHO), pre-mRNA processing factor 31 (PRPF31), retinitis pigmentosa 1 (RP1), and inosine monophosphate dehydrogenase 1 (IMPDH1) genes in Indian patients with isolated and autosomal dominant forms of retinitis pigmentosa (adRP). Information on such data is not available in India and hence this study was undertaken.


METHODS
Blood samples were obtained from 48 isolated and 53 adRP patients, who were recruited for the study. Each patient underwent a detailed clinical examination. Genomic DNA was extracted from the blood samples and screened for mutations in four genes using an ABI3100 Avant genetic analyzer. Reverse transcriptase polymerase chain reaction was performed to amplify the mutated (IVS6+1G/A) mRNA of PRPF31 in a two-generation adRP family.


RESULTS
Of the 101 probands analyzed, three harbored possible disease-causing mutations. Pathogenic changes were observed in RHO and PRPF31. A RHO mutation, p.Gly106Arg, was found in an isolated RP patient with sectoral RP. Two novel, heterozygous mutations were identified in PRPF31: p.Lys120GlufsX122 in an isolated RP patient and a splice site mutation, IVS6+1G/A in an adRP patient. However, no disease-causing changes were observed in RP1 and IMPDH1.


CONCLUSIONS
We screened RHO, PRPF31, RP1, and IMPDH1 and identified causative mutations in 4% of isolated and 2% of adRP patients from India. To the best of our knowledge, this is the first report to identify frequencies of mutations in isolated and adRP patients in India.
Department of Genetics and Molecular Biology, Vision Research Foundation, Sankara Nethralaya Chennai, India. gmamatha5@gmail.com
Mamatha
M
Gandra
Venkataramana
V
Anandula
Vidhya
V
Authiappan
Srilekha
S
Sundaramurthy
Rajiv
R
Raman
Shomi
S
Bhattacharya
Kumaramanickavel
K
Govindasamy
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics*; D007194:India; D007438:Introns / Q000235:genetics; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics*
D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C454222:PRPF31 protein, human; C120042:RP1 protein, human; D012243:Rhodopsin; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human