Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.
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.
Miano
M G
MG
International Institute of Genetics and Biophysics, CNR, Naples, Italy.
Testa
F
F
Filippini
F
F
Trujillo
M
M
Conte
I
I
Lanzara
C
C
Millán
J M
JM
De Bernardo
C
C
Grammatico
B
B
Mangino
M
M
Torrente
I
I
Carrozzo
R
R
Simonelli
F
F
Rinaldi
E
E
Ventruto
V
V
D'Urso
M
M
Ayuso
C
C
Ciccodicola
A
A
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*