TY - JOUR
T1 - Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains
AU - Miano, Maria Giuseppina
AU - Testa, Francesco
AU - Filippini, Francesco
AU - Trujillo, Mariajosè
AU - Conte, Ivan
AU - Lanzara, Carmela
AU - Millán, Josè Maria
AU - De Bernardo, Carmelilia
AU - Grammatico, Barbara
AU - Mangino, Massimo
AU - Torrente, Isabella
AU - Carrozzo, Romeo
AU - Simonelli, Francesca
AU - Rinaldi, Ernesto
AU - Ventruto, Valerio
AU - D'Urso, Michele
AU - Ayuso, Carmen
AU - Ciccodicola, Alfredo
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - MAP domain
KW - Mutation analysis
KW - NM23 domain
KW - Retinal disease
KW - Retinitis pigmentosa 2, X-linked
KW - RP2
KW - XLRP
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U2 - 10.1002/humu.1160
DO - 10.1002/humu.1160
M3 - Article
C2 - 11462235
AN - SCOPUS:0034903235
VL - 18
SP - 109
EP - 119
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 2
ER -