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| Germinal mosaicism is associated with X-linked retinitis pigmentosa: a frequent mutation in the RPGR-ORF15 gene |
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| 作者：Zi-Bing … 文章来源：Department of Ophthalmology & Visual Science, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692 Japan. 点击数1041 更新时间：2006/6/29 18:23:58 文章录入：jinzibing 责任编辑：毛进 |
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| Purpose: To identify mutation in a family with X chromosome linked retinitis pigmentosa (XLRP) and to delineate the phenotypic changes in the patients.
Methods: A three-generation family with retinitis pigmentosa (RP) was recruited and clinical and ophthalmological examinations were performed on the affected and unaffected family members. DNA was extracted from the blood samples. Eight family members were genotyped with microsatellite markers at loci which were considered to be associated with XLRP. RPGR-ORF15 gene was comprehensively screened by using the direct polymerase chain reaction (PCR)-sequencing method.
Results: The proband patients had early onset of night blindness and severely impaired visual acuity whereas his parents were asymptomatic. Haplotype analysis showed that the affected individuals in the family shared a common haplotype with markers DX6810, DXS1068 and DXS8025 at Xp11.3-11.4，encompassing the RPGR locus. Directly PCR-sequencing of RPGR-ORF15 gene identified a homozygous two-base deletion at 652_653 in exon ORF15 in two affected males and a heterozygous mutation in the carrier female. The mutation was predicted to create an early termination at 248 (Gly217fsTer248). The mutation was not observed in 80 normal controls. Interestingly, direct-sequencing of the parents showed the wild-type sequence.
Conclusion: In brief, we first reported a maternal germinal mutation in RPGR gene in a XLRP family in which the mutation was found in two affected sibling patients but the asymptomatic parents. To our knowledge, this mutation is the most frequent mutation in exon ORF15. Thus, screening of ORF15 may help to identify the disease-causing mutation in simplex RP families which is thought to possess more than 50% of nonsyndromic RP. |
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