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 Citations (Scopus)

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

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Hyperlipoproteinemia Type II
LDL Receptors
LDL Cholesterol
Mutation
Xanthomatosis
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Genetic Counseling
Apolipoproteins B
Genetic Testing
Pedigree
Serum
Tendons
Parents
Alleles
Mothers
Skin
DNA
Genes
Ezetimibe

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

Cite this

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title = "Compound heterozygous familial hypercholesterolemia in a Chinese boy with a de novo and transmitted low-density lipoprotein receptor mutation",
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.",
keywords = "Apolipoprotein B-100, DNA sequencing, Familial hypercholesterolemia, Gene mutation, Low-density lipoprotein cholesterol, Low-density lipoprotein receptor, Proprotein convertase subtilisin/kexin type 9",
author = "Yizhe Ma and Yingyun Gong and Abhimanyu Garg and Hongwen Zhou",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.jacl.2017.10.005",
language = "English (US)",
journal = "Journal of Clinical Lipidology",
issn = "1933-2874",
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TY - JOUR

T1 - Compound heterozygous familial hypercholesterolemia in a Chinese boy with a de novo and transmitted low-density lipoprotein receptor mutation

AU - Ma, Yizhe

AU - Gong, Yingyun

AU - Garg, Abhimanyu

AU - Zhou, Hongwen

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Apolipoprotein B-100

KW - DNA sequencing

KW - Familial hypercholesterolemia

KW - Gene mutation

KW - Low-density lipoprotein cholesterol

KW - Low-density lipoprotein receptor

KW - Proprotein convertase subtilisin/kexin type 9

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