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
N1 - Funding Information:
This work was supported by the National Natural Sciences Foundation of China (grant number 81670723); the Natural Science Foundation of Jiangsu Province (grant number BK20161589) and the State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University (grant number KF-GN-201502) in data collection, analysis, and interpretation; and the Key Medical Talents Fund of Jiangsu Province (ZDRCA2016017) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD; grant number JX10231801) in the decision to submit the article for publication.
Publisher Copyright:
© 2017 National Lipid Association
PY - 2018/1
Y1 - 2018/1
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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U2 - 10.1016/j.jacl.2017.10.005
DO - 10.1016/j.jacl.2017.10.005
M3 - Article
C2 - 29233637
AN - SCOPUS:85037670111
VL - 12
SP - 230-235.e6
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
SN - 1933-2874
IS - 1
ER -