Scientific Publication Independent computational study on novel mutation correlated to FH
A novel pathogenic variant of the LDLR gene in the Asian population and its clinical correlation with familial hypercholesterolemia J. K. Chahil et al. (2012) Mol Biol Rep 39(7): 7831-7838
Full article published in:
Molecular Biology Reports Familial hypercholesterolemia (FH) is a disease implicated with defects in either, Low density lipoprotein receptor gene (LDLR), Apolipoprotein B-100 gene (APOB), the Proprotein convertase subtilisin/kexin type 9 gene (PCSK9) or other related genes of the lipid metabolism pathway. The general characterization of heterozygous FH is by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular diseases, while the more severe type, the homozygous FH results in extreme elevated levels of LDL cholesterol and usually death of an affected individual by early twenties.
This project was supported by the Ministry of Science, Technology and Innovation (MOSTI), the government of Malaysia. A novel nonsynonymous, missense mutation in exon 14 of the LDLR gene in two siblings of the Malay ethnicity was discovered during an in-house genetic test. This report postulates their elevated cholesterol is due to this novel mutation and they are positive for homozygous FH. This is the first report of a C711Y mutation in patients with elevated cholesterol in Asia. The novel discovery of this mutation is included in the commercially available INFOHaem microarray chip FH1536TM.
(A) Structure prediction of the wildtype sequence. The Cys711 residue is found to be the 6755th atom of this structure containing a total of 8178 atoms. (B) Structure prediction of the mutant sequence. The Tyr711 residue is found to be the 6758th atom of this structure containing a total of 8184 atoms.
The differences in the structures of wildtype (A) and mutant protein (B).
Š 2012 INFOVALLEY. www.infovalley.net.my