Objectives Familial hypercholesterolemia (FH) is an autosomal dominant hypercholesterolemia caused by mutation in the low density lipoprotein receptor gene (LDLR). The identification of the causative mutation provides definitive diagnosis so that the patient can be treated, their relatives tested and, therefore, premature heart disease prevented.

Methods DNA of the proband with clinically diagnosed FH and other three familial members were analysed using polymerase chain reaction (PCR) and DNA direct sequencing for the LDLR gene (promoter region, the translated exon sequences, and the exon-intron boundaries), the apolipoprotein B-100 gene (APOB) (part exon 26). TA cloning was performed to confirm the deletion mutations of the exon 11 of LDLR of the proband. Splice site prediction tools were used to predict the effect of a genetic variant on splicing. In addition unaffected random controls (n = 100) were screened the deleltion mutations (c. 1587_1588delCT and c. 1587-2_1587-4delCCA) of LDLR using PCR and sequencing.

Results In this Chinese family, two heterozygous novel mutation (c. 1587_1588delCT and c. 1587-2_1588-4delCCA) of the LDLR were found in the proband and his mother, but no deletion mutations were detected in his father and his sister. The two-bases deletion of CT (1587_1588del2) at exon 11 is a frameshift mutation which predicted to be pathogenic. The functional effect of another novel mutation at intron 10 (c. 1587-2_1588-4delCCA) are predicted as benign by splice site prediction tools.

Conclusions Only mutation in exon 11 of LDLR gene (c. 1587_1588delCT) had been found to cause FH, which was novel, not described in other FH populations.