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 language | English (US) |
|---|---|
| Journal | Journal of Clinical Lipidology |
| DOIs | |
| State | Accepted/In press - Jan 1 2017 |
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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
Compound heterozygous familial hypercholesterolemia in a Chinese boy with a de novo and transmitted low-density lipoprotein receptor mutation. / Ma, Yizhe; Gong, Yingyun; Garg, Abhimanyu; Zhou, Hongwen.
In: Journal of Clinical Lipidology, 01.01.2017.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85037670111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85037670111&partnerID=8YFLogxK
U2 - 10.1016/j.jacl.2017.10.005
DO - 10.1016/j.jacl.2017.10.005
M3 - Article
C2 - 29233637
AN - SCOPUS:85037670111
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
SN - 1933-2874
ER -