title: Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.
abstract: X-linked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity with almost five distinct loci on the X chromosome. So far, only two XLRP genes have been identified, RPGR (or RP3) and RP2, being mutated in approximately 70% and 10% of the XLRP patients. Clinically there is no clearly significative difference between RP3 and RP2 phenotypes. In the attempt to assess the degree of involvement of the RP2 gene, we performed a complete mutation analysis in a cohort of patients and we identified five novel mutations in five different XLRP families. These mutations include three missense mutations, a splice site mutation, and a single base insertion, which, because of frameshift, anticipates a stop codon. Four mutations fall in RP2 exon 2 and one in exon 3. Evidence that such mutations are different from the 21 RP2 mutations described thus far suggests that a high mutation rate occurs at the RP2 locus, and that most mutations arise independently, without a founder effect. Our mutation analysis confirms the percentage of RP2 mutations detected so far in populations of different ethnic origin. In addition to novel mutations, we report here that a deeper sequence analysis of the RP2 product predicts, in addition to cofactor C homology domain, further putative functional domains, and that some novel mutations identify RP2 amino acid residues which are evolutionary conserved, hence possibly crucial to the RP2 function.
authors.affiliation: International Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Miano
authors.forename: F
authors.initials: F
authors.lastname: Testa
authors.forename: F
authors.initials: F
authors.lastname: Filippini
authors.forename: M
authors.initials: M
authors.lastname: Trujillo
authors.forename: I
authors.initials: I
authors.lastname: Conte
authors.forename: C
authors.initials: C
authors.lastname: Lanzara
authors.forename: J M
authors.initials: JM
authors.lastname: Millán
authors.forename: C
authors.initials: C
authors.lastname: De Bernardo
authors.forename: B
authors.initials: B
authors.lastname: Grammatico
authors.forename: M
authors.initials: M
authors.lastname: Mangino
authors.forename: I
authors.initials: I
authors.lastname: Torrente
authors.forename: R
authors.initials: R
authors.lastname: Carrozzo
authors.forename: F
authors.initials: F
authors.lastname: Simonelli
authors.forename: E
authors.initials: E
authors.lastname: Rinaldi
authors.forename: V
authors.initials: V
authors.lastname: Ventruto
authors.forename: M
authors.initials: M
authors.lastname: D'Urso
authors.forename: C
authors.initials: C
authors.lastname: Ayuso
authors.forename: A
authors.initials: A
authors.lastname: Ciccodicola
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015331:Cohort Studies; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D012174:Retinitis Pigmentosa / Q000235:genetics*; D016415:Sequence Alignment; D017385:Sequence Homology; D014960:X Chromosome / Q000235:genetics*