Compound heterozygous familial hypercholesterolemia in a Chinese boy with a de novo and transmitted low-density lipoprotein receptor mutation.

BACKGROUND

Homozygous familial hypercholesterolemia is characterized by extremely elevated serum low-density lipoprotein cholesterol (LDL-C) levels and increased risk of cardiovascular complications due to biallelic mutations in LDL receptor (LDLR).

OBJECTIVE

We present a 10-year-old Chinese homozygous familial hypercholesterolemia boy with biallelic LDLR mutations including an extremely rare de novo mutation.

METHODS

Detailed family history and clinical and biochemical data were gathered from the pedigree. Genomic DNA was isolated and the reported LDL-related genes (LDLR, APOB, PCSK9, ABCG5, ABCG8, ANGPTL3, APOC3, and LDLRAP1) were sequenced.

RESULTS

The proband displayed extensive cutaneous and tendon xanthomas together with elevated serum LDL-C level of 14.87 mmol/L (575 mg/dL). A combination of simvastatin 40 mg daily and ezetimibe 10 mg daily resulted in 57% lowering of LDL-C. The proband had compound heterozygous LDLR disease-causing mutations, including p.(His583Tyr) variant transmitted from the mother and a de novo p.(Gln242*) variant on the paternal allele.

CONCLUSIONS

Our report supports the role of genetic testing in the proband and the parents for accurate genetic counseling. Our patient had marked lowering of LDL-C with a combination of statin and ezetimibe but may require additional therapy.