Mutational analysis of RPGR and RP2 genes in Japanese patients with retinitis pigmentosa: identification of four mutations.
OBJECTIVE
To identify mutations in RPGR and RP2 genes in a series of Japanese retinitis pigmentosa (RP) families and to determine the association between the phenotypic changes in patients/carriers and the mutations.


METHODS
A total of 37 unrelated RP families were recruited, three of which were with typical X-linked RP (XLRP), and other 34 families included 29 multiplex families and 5 simplex RP cases with no family history of RP. In addition, At least one RP patient had myopia >-3.0D in these families. RPGR and RP2 genes were comprehensively screened by using the direct polymerase chain reaction-sequencing method. Detailed phenotypes of the families with confirmed mutations were assessed by routine ophthalmic examinations, Goldmann perimetry, electroretinography and color fundus photography.


RESULTS
Four mutations in RPGR and RP2 genes were identified. Of the three XLRP families, one had an ORF15 mutation and another had an RP2 mutation. Two ORF15 mutations were found in three of the other 34 RP families, with two families sharing a same mutation, g.ORF15+652-653delAG. All the three ORF15 mutations were first reported in the Japanese population. Affected males showed relatively severe symptoms while female carriers showed a wide spectrum of severity. A tapetal-like reflex was observed in two young females, indicating clinically the carrier status.


CONCLUSIONS
We identified three ORF15 mutations and one RP2 mutation in five Japanese RP families. Moderate or severe myopia might be an indicator for the XLRP status in multiplex RP families which pedigree data are insufficient to allow accurate subtyping. It is suggested that mutational analysis of RPGR and RP2 may help to identify the causative mutation in a proportion of multiplex RP patients with myopia.
Jin
Zi-Bing
ZB
Department of Ophthalmology and Visual Science, Faculty of Medicine, The University of Miyazaki, Miyazaki, Japan. jinzb@med.miyazaki-u.ac.jp <jinzb@med.miyazaki-u.ac.jp>
Liu
Xiao-Qiang
XQ
Hayakawa
Mutsuko
M
Murakami
Akira
A
Nao-i
Nobuhisa
N
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005654:Fundus Oculi; D019204:GTP-Binding Proteins; D017353:Gene Deletion; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017421:Sequence Analysis; D012720:Severity of Illness Index; D012737:Sex Factors
D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; C099929:RPGR protein, human; D019204:GTP-Binding Proteins