Analysis of LDLR mRNA in patients with familial hypercholesterolemia revealed a novel mutation in intron 14, which activates a cryptic splice site

Journal of Human Genetics

Volumn 55, Issue 10, 2010, Pages 676-680

  Kulseth, Mari Ann ^a   Berge, Knut Erik ^a   Bogsrud, Martin Prøven ^a   Leren, Trond P ^a  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

Author keywords

c.2140+86; cryptic splice site; familial hypercholesterolemia; FH; LDLR

Indexed keywords

AMINO ACID; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; MESSENGER RNA;

ARTICLE; BASE PAIRING; BLOOD SAMPLING; CHOLESTEROL BLOOD LEVEL; DNA SEQUENCE; ENDOPLASMIC RETICULUM; EXON; FAMILIAL HYPERCHOLESTEROLEMIA; GENE MUTATION; GENETIC ANALYSIS; GENETIC DISORDER; HUMAN; INTRON; PROTEIN FOLDING; RNA EXTRACTION; RNA SPLICING;

EXONS; FEMALE; HUMANS; HYPERCHOLESTEROLEMIA; HYPERLIPOPROTEINEMIA TYPE II; INTRONS; MALE; MUTATION; PEDIGREE; RECEPTORS, LDL; RNA SPLICE SITES; RNA, MESSENGER;

EID: 78049258389     PISSN: 14345161     EISSN: None     Source Type: Journal    
DOI: 10.1038/jhg.2010.87     Document Type: Article

References (16)

1. Stenson, P., Mort, M., Ball, E., Howells, K., Phillips, A., Thomas, N. et al. The Human Gene Mutation Database: 2008 update. Genome Med. 1, 13(2009).
2. Hobbs, H. H., Brown, M. S. & Goldstein, J. L. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum. Mutat. 1, 445-466 (1992).
3. Holla, O. L., Teie, C., Berge, K. E. & Leren, T. P. Identification of deletions and duplications in the low density lipoprotein receptor gene by MLPA. Clin. Chim. Acta 356, 164-171 (2005). (Pubitemid 40779898)
4. Sozen, M., Whittall, R. & Humphries, S. E. Mutation detection in patients with familial hypercholesterolaemia using heteroduplex and single strand conformation polymorphism analysis by capillary electrophoresis. Atheroscler. Suppl. 5, 7-11 (2004). (Pubitemid 39535760)
5. Behm-Ansmant, I., Kashima, I., Rehwinkel, J., Sauliere, J., Wittkopp, N. & Izaurralde, E. mRNA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons. FEBS Lett. 581, 2845-2853 (2007). (Pubitemid 46874393)
6. Tveten, K., Ranheim, T., Berge, K. E., Leren, T. P. & Kulseth, M. A. Analysis of alternatively spliced isoforms of human LDL receptor mRNA. Clin. Chim. Acta 373, 151-157 (2006). (Pubitemid 44292194)
7. Sørensen, S., Ranheim, T., Bakken, K. S., Leren, T. P. & Kulseth, M. A. Retention of mutant low density lipoprotein receptor in endoplasmic reticulum (ER) leads to ER stress. JBC 281, 468-476 (2006). (Pubitemid 43671209)
8. Yeo, G. & Burge, C. B. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J. Comput. Biol. 11, 377-394 (2004). (Pubitemid 38901668)
9. Tveten, K., Holla, O. L., Ranheim, T., Berge, K. E., Leren, T. P. & Kulseth, M. A. 4-Phenylbutyrate restores the functionality of a misfolded mutant low-density lipoprotein receptor. FEBS J. 274, 1881-1893 (2007). (Pubitemid 46587991)
10. Tolleshaug, H., Goldstein, J. L., Schneider, W. J. & Brown, M. S. Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia. Cell 30, 715-724 (1982). (Pubitemid 13204661)
11. Engel, K., Nuoffer, J. M., Muhlhausen, C., Klaus, V., Largiader, C. R., Tsiakas, K. et al. Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency. Mol. Genet. Metab. 94, 292-297 (2008).
12. Baralle, D., Lucassen, A. & Buratti, E. Missed threads. The impact of pre-mRNA splicing defects on clinical practice. EMBO Rep. 10, 810-816 (2009).
13. Sullivan, P. F., Fan, C. & Perou, C. M. Evaluating the comparability of gene expression in blood and brain. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141 B, 261-268 (2006).
14. Spurdle, A. B., Couch, F. J., Hogervorst, F. B., Radice, P. & Sinilnikova, O. M. Prediction and assessment of splicing alterations: implications for clinical testing. Hum. Mutat. 29, 1304-1313 (2008).
15. Wang, Z. & Burge, C. B. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 14, 802-813 (2008). (Pubitemid 351574901)
16. Vorechovsky, I. Transposable elements in disease-associated cryptic exons. Hum. Genet. 127, 135-154 (2010).