| Autor: |
Waanders E; Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands., Venselaar H, te Morsche RH, de Koning DB, Kamath PS, Torres VE, Somlo S, Drenth JP |
| Jazyk: |
angličtina |
| Zdroj: |
Clinical genetics [Clin Genet] 2010 Jul; Vol. 78 (1), pp. 47-56. Date of Electronic Publication: 2010 Jan 20. |
| DOI: |
10.1111/j.1399-0004.2009.01353.x |
| Abstrakt: |
Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein structure and function. We screened 464 subjects including 76 probands by direct sequencing or conformation-sensitive capillary electrophoresis. We analyzed the effects of all known and novel mutations using a combination of splice site recognition, evolutionary conservation, secondary and tertiary structure predictions, PolyPhen, and pMut and sift. We identified a total of 26 novel mutations in PRKCSH (n = 14) and SEC63 (n = 12), including four splice site mutations, eight insertions/ deletions, six non-sense mutations, and eight missense mutations. Out of 48 PCLD mutations, 13 were predicted to affect splicing. Most mutations were located in highly conserved regions and homology modeling for two domains of Sec63p showed severe effects of the residue substitutions. In conclusion, we identified 26 novel mutations associated with PCLD and we provide in silico analysis in order to delineate the role of these mutations. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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