ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis pigmentosa.
OBJECTIVE
To evaluate photoreceptor cell-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) gene mutations in Japanese patients with Stargardt disease (STGD) and the correlation of these mutations to clinical phenotypes.


METHODS
Serum was obtained from 10 unrelated Japanese patients with STGD and 96 unrelated Japanese patients with autosomal recessive retinitis pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were screened for mutations by a combination of single-strand conformation polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing techniques. By restriction enzyme digestion, primer extension analysis, and PCR direct sequencing techniques, the patients with arRP were screened for three segregated, presumably null ABCA4 gene mutations observed in Japanese patients with STGD.


RESULTS
Three novel, presumably null mutations of the ABCA4 gene, IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The Arg2149stop mutation that had been found in a white patient with STGD in a prior study was also found in a Japanese patient. Two arRP-affected siblings and two unrelated patients with STGD were found to be homozygous for the same IVS12+2T-->G mutation, and three other arRP-affected siblings were carriers of the IVS12+2T-->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three siblings with arRP showed only atrophic degeneration in the macula early after the onset of the disease, and STGD had been diagnosed.


CONCLUSIONS
Three novel ABCA4 gene mutations were identified in Japanese patients with STGD and arRP. Mutations in the ABCA4 gene can cause panretinal degeneration that changes its clinical appearance from STGD to arRP over time.
Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
Takehiro
T
Fukui
Shuji
S
Yamamoto
Kaoru
K
Nakano
Motokazu
M
Tsujikawa
Hiroyuki
H
Morimura
Koji
K
Nishida
Nobuyuki
N
Ohguro
Takashi
T
Fujikado
Motohiro
M
Irifune
Kazuki
K
Kuniyoshi
Annabelle A
AA
Okada
Akito
A
Hirakata
Yozo
Y
Miyake
Yasuo
Y
Tano
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D004596:Electroretinography; D005091:Exons; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007564:Japan; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters