کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5719386 | 1607415 | 2017 | 11 صفحه PDF | دانلود رایگان |
ObjectiveTo evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia.Study designLDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4â±â3.7 years) with clinically diagnosed FH. The presence of polygenic hypercholesterolemia was further evaluated by genotyping 6 low-density lipoprotein cholesterol (LDL-C)-raising single-nucleotide polymorphisms.ResultsThirty-nine children (50.0%) were found to carry LDLR mutant alleles but none with APOB or PCSK9 mutant alleles. Overall, 27 different LDLR mutations were identified, and 2 were novel. Children carrying mutations showed higher LDL-C (215.2â±â52.7âmg/dL vs 181.0â±â44.6âmg/dL, Pâ<.001) and apolipoprotein B levels (131.6â±â38.3âmg/dL vs 100.3â±â30.0âmg/dL, Pâ<.004), compared with noncarriers. A LDL-C of ~190âmg/dL was the optimal value to discriminate children with and without LDLR mutations. When different diagnostic criteria were compared, those proposed by the European Atherosclerosis Society showed a reasonable balance between sensitivity and specificity in the identification of LDLR mutations. In children without mutation, the FH phenotype was not caused by the aggregation of LDL-C raising single-nucleotide polymorphisms.ConclusionsIn unselected children with hypercholesterolemia, LDL-C levels >190âmg/dL and a positive family history of hypercholesterolemia appeared to be the most reliable criteria for detecting FH. As 50% of children with suspected FH did not carry FH-causing mutations, genetic testing should be considered.
Journal: The Journal of Pediatrics - Volume 183, April 2017, Pages 100-107.e3