Mutation analysis of the RPGR gene reveals novel mutations in south European patients with X-linked retinitis pigmentosa

Miano, Maria Giuseppina; Testa, Francesco; Strazzullo, Maria; Trujillo, M.J.; C, De Bernardo; Grammatico, Barbara; Simonelli, Francesca; Mangino, Massimo; Torrente, Isabella; Ruberto, Giulio; Beneyto, Magdalena; Antiñolo, Guillermo; Rinaldi, E; Danesino, Cesare; Ventruto,; D’Urso, Michele; Ayuso, Carmen; Baiget, Montserrat; Ciccodicola, Alfredo

doi:10.1038/sj.ejhg.5200352

Cited by 30 publications

(30 citation statements)

References 23 publications

(39 reference statements)

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“…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%

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: 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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“…The proportion of mutations identified in RPGR in this population now agrees with that predicted by linkage analysis. Although a different RP3 locus closely linked to RPGR cannot be excluded, a high frequency of ORF15 mutations has been found in ongoing studies in other populations [Miano et al, 2001;Rabe et al, 2001] (Table 1). Further exon ORF15 mutations have been found by Mears et al [2000], Aguirre et al [2001], and Nao-i et al [2001], although the proportion of XLRP patients remains to be established.…”

Section: Mutation Screening Of Exon Orf15mentioning

confidence: 99%

Mutations ofRPGR in X-linked retinitis pigmentosa (RP3)

Vervoort

Wright

2002

Hum. Mutat.

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Mutations in RPGR, retinitis pigmentosa GTPase regulator, are associated with RP3 type of Xlinked retinitis pigmentosa, a severe, non-syndromic form of retinal degeneration. In the majority of subjects RPGR mutations are associated with a typical rod-cone degeneration, but in a small number, cone-rod dystrophy, deafness, and abnormalities in respiratory cilia have been noted. Alternative splicing of RPGR is complex in all species examined. In RP3 patients, mutations have been found in exons 1 14 and ORF15, thus delineating a transcript necessary for normal retinal function in humans. The great majority of mutations are predicted to result in premature termination of translation. These mutations are scattered over exons 1 14 and ORF15, while most missense mutations occur in a domain with homology to the protein RCC1, encoded by exons 1 10. Exon ORF15 is a hot spot for mutation, at least in the British population, in which it harbors 80% of the mutations found within a sample of 47 X-linked retinitis pigmentosa patients. Most RPGR mutations are unique to single families, which makes it difficult to demonstrate phenotype genotype correlations. Hum Mutat 19:486 500, 2002.

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“…There have been only 3 studies examining the molecular epidemiology of specific forms of RP in Italy: a study on 43 adRP families (Ziviello et al, 2005), a characterization of 75 families with Usher syndrome (Vozzi et al, 2011), and a report on 15 familial cases of XL-RP (Miano et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…A previous study examined 15 Italian families with XL-RP (Miano et al, 1999), but the ORF15 region, which was identified in a later study (Vervoort et al, 2000), was not screened. We therefore report the results of molecular screening of the ORF15 exon in Italian families for the first time.…”

Section: Discussionmentioning

confidence: 99%

Syndromic and non-syndromic forms of retinitis pigmentosa: a comprehensive Italian clinical and molecular study reveals new mutations

Pierrottet¹,

Zuntini²,

Digiuni³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Mutations in more than 60 different genes have been associated with non-syndromic and syndromic retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies. To increase the understanding of the molecular epidemiology of the disease in Italy, we analyzed 56 patients with syndromic and non-syndromic forms of RP attending the Retinitis Pigmentosa Center of San Paolo Hospital (Milan, Italy). Patients underwent detailed clinical examination. Genomic DNA isolated from peripheral blood samples was screened for mutations in different genes according to RP form by direct sequencing analysis. The impact of novel missense mutations on protein functions was predicted by in silico analysis and protein sequence alignment. Cosegregation analysis was performed between available family members. Forty-one of the 56 probands analyzed had non-syndromic and 15 had syndromic RP forms. Putative disease-causing mutations were identified in 19 of 56 unrelated RP probands. Mutation screening identified a total of 22 different heterozygous variants. Notably, 12 of these putative pathogenic mutations have not been previously reported. New variants were found to be located on the USH2A, RPGR, EYS, and RHO genes. All 3 new variants detected in X-linked RP probands were confirmed in other affected family members. We found a positivity rate of 24.4% and 60% for probands with non-syndromic and syndromic RP, respectively. This is the first report of RPGR X-linked RP proband-ORF15 mutations in Italian patients with X-linked (XL)-RP. In addition, this is the first report of data regarding the association between EYS mutations and non-syndromic RP forms in the Italian population.

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Mutation analysis of the RPGR gene reveals novel mutations in south European patients with X-linked retinitis pigmentosa

Cited by 30 publications

References 23 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

Mutations ofRPGR in X-linked retinitis pigmentosa (RP3)

Syndromic and non-syndromic forms of retinitis pigmentosa: a comprehensive Italian clinical and molecular study reveals new mutations

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