Mutations in the RP2 Gene Cause Disease in 10% of Families with Familial X-Linked Retinitis Pigmentosa Assessed in This Study

Hardcastle, Alison J.; Thiselton, Dawn L.; Maldergem, Lionel Van; Saha, Bratin K.; Jay, Marcelle; Plant, Catherine; Taylor, Rachel; Bird, Alan C.; Bhattacharya, Siladitya

doi:10.1086/302325

Cited by 91 publications

(68 citation statements)

References 11 publications

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“…Altogether, the frequency of RPGR and RP2 mutations in French XLRP families is in accordance with that reported in other studies (RP2: 15.9% vs. 6-20% [Schwahn et al, 1998;Hardcastle et al, 1999;Mears et al, 1999;Thiselton et al, 2000;Miano et al, 2001;Breuer et al, 2002;Sharon et al, 2003]; RPGR: 78.4% vs. 55-90% [Roepman et al, 1996;Meindl et al, 1996;Zito et al, 1999;Vervoort et al, 2000;Buraczynska et al, 1997;Vervoort and Wright 2002;Demirci et al, 2002;Breuer et al, 2002;Sharon et al, 2003]). …”

Section: Discussionsupporting

confidence: 92%

“…A number of studies have reported mutations in XLRP genes [Schwahn et al, 1998;Hardcastle et al, 1999;Mears et al, 1999;Thiselton et al, 2000;Miano et al, 1999Miano et al, , 2001Breuer et al, 2002;Sharon et al, 2000Roepman et al, 1996Meindl et al, 1996;Vervoort et al, 2000;Zito et al, 1999;Buraczynska et al, 1997;Vervoort and Wright 2002;Demirci et al, 2002]. These mutations have recently been referenced in the Human Gene Database.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype–phenotype correlations and impact on genetic counseling

et al. 2006

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Communicated by Daniel F. Schorderet X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of families with RP and are mainly accounted for by mutations in the RP2 or RP GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked inheritance, including 48 out of 93 families with expression in females but no male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP families excluded linkage to the RP2 and RP3 loci and were removed form the cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14 out of 88 familial cases of RP and 1 out of 25 sporadic male case (4%). In 13 out of 14 of the familial cases, no expression of the disease was noted in females, while in 1 out of 14 families one woman developed RP in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%); 8 out of 25 sporadic male cases (32.0%); and 1 out of 2 COD. No expression of the disease was noted in females in 41 out of 69 familial cases (59.4%), while at least one severely affected woman was recognized in 28 out of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP suggestive of X-linked transmission are in accordance to that reported elsewhere . Interestingly, about 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years. Hum Mutat 28(1), [81][82][83][84][85][86][87][88][89][90][91] 2007.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype–phenotype correlations and impact on genetic counseling

et al. 2006

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“…Even in Mendelian disorders such as X-linked retinitis pigmentosa (RP) and familial breast cancer, single genes are involved in only 10% and 5% of the cases, respectively (Hardcastle et al 1999). Multifactorial diseases such as diabetes, obesity, and Alzheimer disease have a population frequency greater than 1% and differ from single-gene diseases such as cystic fibrosis and muscular dystrophy.…”

Section: Discussionmentioning

confidence: 99%

Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity

et al. 2001

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Retinopathy of prematurity (ROP) is a leading cause of blindness in premature children. It is a multifactorial disorder which causes fibrovascular tissue changes that affect the retina in low birth-weight and short gestational age infants. To determine the prevalence of Norrie disease (ND) gene mutations, clinical examination and molecular genetic analyses were performed in 100 pre-term babies of different ethnic backgrounds who developed advanced ROP. The leukocyte DNA was extracted, amplified by the polymerase chain reaction (PCR), and analyzed by singlestrand conformation polymorphism (SSCP), G/T and C/A scanning, and by DNA sequencing. All three exons, including splice sites and the 3Ј-untranslated region, were screened. Of the 100 patients analyzed, 2 patients with advanced ROP showed a mobility shift in the DNA. In 1 patient, this mobility shift was caused by the insertion of an additional 12-bp CT repeat in exon 1, and in the second patient, there was a 14-bp deletion in the same exon of the ND gene, as evidenced by direct sequencing of the amplified products. Similar analyses of exons 2 and 3 and the 3Ј-untranslated region failed to detect additional mutations in the gene. None of the 130 normal, unrelated controls revealed similar changes. Taking into account the above results, as well as those of other studies, it appears that the ND gene mutations can account for 3% of cases of advanced ROP. Although the ND gene is not frequently involved in advanced ROP, the present large-scale study further supports the hypothesis that genetic influences may play an important role in the development of severe ROP in some premature infants.

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“…In XLRP, it has been suggested that RP2 and RP3 represent the two predominant forms (Teague et al 1994). Mutational analysis of the RPGR and RP2 genes together accounted for approximately 30% of familial XLRP cases (Hardcastle et al 1999;Mears et al 1999) mapped to these genetic loci. This still leaves about 70% of cases unaccounted for.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of RP2 and RP3 genes in an X-linked RP family manifesting loss of central vision and preserved peripheral function

2001

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X-Linked retinitis pigmentosa is a most severe and heterogeneous disorder of the retina. Recently, genes (RP2 and RPGR) from two X-linked loci have been positionally cloned and mutations have been identified in many families. To further evaluate allelic and non-allelic heterogeneity and the genotype -phenotype relationships, and to determine the prevalence of mutations in the gene, we have analyzed one previously unreported X-linked retinitis pigmentosa family, using a combination of haplotype analysis and DNA sequencing. Our extensive analysis of the RP2 gene failed to detect any disease -causing or polymorphic mutations. In the case of the RP3 gene, the alleles of the dinucleotide repeat marker did not segregate with the disease. Although we cannot completely exclude the possibility of the RP2 and RP3 genes as candidate genes, the above results suggest that structural and functional changes associated with the RP2 gene are not responsible for the phenotype in the family analyzed. Further identification of the X-linked genes may facilitate the elucidation of the molecular basis of the disorder in the family analyzed.

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Mutations in the RP2 Gene Cause Disease in 10% of Families with Familial X-Linked Retinitis Pigmentosa Assessed in This Study

Cited by 91 publications

References 11 publications

Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype–phenotype correlations and impact on genetic counseling

Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype–phenotype correlations and impact on genetic counseling

Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity

Evaluation of RP2 and RP3 genes in an X-linked RP family manifesting loss of central vision and preserved peripheral function

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