Objective To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia. Study design LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 ± 3.7 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. Results Thirty-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 (215.2 ± 52.7 mg/dL vs 181.0 ± 44.6 mg/dL, P < .001) and apolipoprotein B levels (131.6 ± 38.3 mg/dL vs 100.3 ± 30.0 mg/dL, P < .004), compared with noncarriers. A LDL-C of ~190 mg/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. Conclusions In unselected children with hypercholesterolemia, LDL-C levels >190 mg/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

Analysis of Children and Adolescents with Familial Hypercholesterolemia / Minicocci, Ilenia; Pozzessere, Simone; Prisco, Cristina; Montali, Anna; Di Costanzo, Alessia; Martino, Eliana; Martino, Francesco; Arca, Marcello. - In: THE JOURNAL OF PEDIATRICS. - ISSN 0022-3476. - STAMPA. - 183:(2017), pp. 100-107.e3. [10.1016/j.jpeds.2016.12.075]

Analysis of Children and Adolescents with Familial Hypercholesterolemia

MINICOCCI, ILENIA;POZZESSERE, SIMONE;PRISCO, CRISTINA;MONTALI, Anna;DI COSTANZO, ALESSIA;MARTINO, ELIANA;MARTINO, Francesco;ARCA, Marcello
2017

Abstract

Objective To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia. Study design LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 ± 3.7 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. Results Thirty-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 (215.2 ± 52.7 mg/dL vs 181.0 ± 44.6 mg/dL, P < .001) and apolipoprotein B levels (131.6 ± 38.3 mg/dL vs 100.3 ± 30.0 mg/dL, P < .004), compared with noncarriers. A LDL-C of ~190 mg/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. Conclusions In unselected children with hypercholesterolemia, LDL-C levels >190 mg/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
children; familial hypercholesterolemia; Genetics; LDL receptor gene; screening; Pediatrics, Perinatology and Child Health
01 Pubblicazione su rivista::01a Articolo in rivista
Analysis of Children and Adolescents with Familial Hypercholesterolemia / Minicocci, Ilenia; Pozzessere, Simone; Prisco, Cristina; Montali, Anna; Di Costanzo, Alessia; Martino, Eliana; Martino, Francesco; Arca, Marcello. - In: THE JOURNAL OF PEDIATRICS. - ISSN 0022-3476. - STAMPA. - 183:(2017), pp. 100-107.e3. [10.1016/j.jpeds.2016.12.075]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/975394
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