Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25757501
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Splicing defects caused by exonic mutations in PKD1 as a new mechanism of
pathogenesis in autosomal dominant polycystic kidney disease
#MMPMID25757501
Claverie-Martin F
; Gonzalez-Paredes FJ
; Ramos-Trujillo E
RNA Biol
2015[]; 12
(4
): 369-74
PMID25757501
show ga
The correct splicing of precursor-mRNA depends on the actual splice sites plus
exonic and intronic regulatory elements recognized by the splicing machinery.
Surprisingly, an increasing number of examples reveal that exonic mutations
disrupt the binding of splicing factors to these sequences or generate new splice
sites or regulatory elements, causing disease. This contradicts the general
assumption that missense mutations disrupt protein function and that synonymous
mutations are merely polymorphisms. Autosomal dominant polycystic kidney disease
(ADPKD) is a common inherited disorder caused mainly by mutations in the PKD1
gene. Recently, we analyzed a substantial number of PKD1 missense or synonymous
mutations to further characterize their consequences on pre-mRNA splicing. Our
results showed that one missense and 2 synonymous mutations induce significant
defects in pre-mRNA splicing. Thus, it appears that aberrant splicing as a result
of exonic mutations is a previously unrecognized cause of ADPKD.
free
free
free
