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

Yizhe Ma, Yingyun Gong, Abhimanyu Garg, Hongwen Zhou

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalJournal of Clinical Lipidology
DOIs
StateAccepted/In press - Jan 1 2017

Keywords

  • Apolipoprotein B-100
  • DNA sequencing
  • Familial hypercholesterolemia
  • Gene mutation
  • Low-density lipoprotein cholesterol
  • Low-density lipoprotein receptor
  • Proprotein convertase subtilisin/kexin type 9

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

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