Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred

Spina, Rossella; Noto, Davide; Barbagallo, Carlo M.; Monastero, Roberto; Ingrassia, V.; Valenti, Vincenza; Baschi, Roberta; Pipitone, Antonina; Giammanco, Antonina; Spada, Maria; Misiano, Gabriella; Scrimali, C.; Cefalù, Angelo B.; Averna, Maurizio

doi:10.1016/j.jacl.2017.10.014

Cited by 8 publications

(3 citation statements)

References 21 publications

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“…Hence, our study provides an approximation to the prevalence of this disease in a population with wide genetic heterogeneity. This prevalence is in agreement with recently published data from the Sicilian population, with a c.432insA (p.H144QfsX26) mutation carrier status of 1:2500 [16]. Furthermore, except for two siblings, the ARH cases in Spain are unrelated and come from geographically spread Spanish regions.…”

Section: Discussionsupporting

confidence: 91%

Autosomal recessive hypercholesterolemia in Spain

et al. 2018

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Section: Discussionsupporting

confidence: 91%

Autosomal recessive hypercholesterolemia in Spain

et al. 2018

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“…Among patients admitted to rehabilitation and secondary prevention programmes, FH prevalence was 1:27 [58]. Data from Sardinia and Sicily, two insular regions, reported a 1:2500 rate of ARH1 mutation carriers (1:140,000 homozygous) [59]. Patients are generally referred to lipid clinics [60].…”

Section: Italymentioning

confidence: 99%

Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

et al. 2018

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The EAS FHSC is an international initiative involving a network of investigators interested in FH from around 70 countries.• Information on FH prevalence is lacking in most countries; where available, data tend to align with contemporary estimates.• FH diagnosis and management varies widely across countries, with overall suboptimal identification and under-treatment.• In most countries diagnosis primarily relies on DLCN criteria, and less frequently on Simon Broom or MEDPED.• Therapy for FH is not universally reimbursed, and criteria vary across countries. Access to PCSK9i and apheresis is limited.

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“…Up to now, LDLR gene occupies the majority among the known causative mutations (90–95%), with APOB for 5–10% and PCSK9 for less than 3% [ 4 ]. Furthermore, rare proportion of FH is caused by the mutations in the LDLRAP1 gene with two pathological variants in autosomal recessive pattern [ 5 ]. To date, more genes including STAP1, APOE, and LIPA have been identified as possible FH-causing genes [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation

Sun

Zhou

et al. 2018

Lipids Health Dis

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BackgroundAlthough there have been many reports in the genetics of familial hypercholesterolemia (FH) worldwide, studies in regard of Chinese population are lacking. In this multi-center study, we aim to characterize the genetic spectrum of FH in Chinese population, and examine the genotype-phenotype correlations in detail.MethodsA total of 285 unrelated index cases from China with clinical FH were consecutively recruited. Next-generation sequencing and bioinformatics tools were used for mutation detection of LDLR, APOB and PCSK9 genes and genetic analysis.ResultsOverall, the detection rate is 51.9% (148/285) in the unrelated index cases with a total of 119 risk variants identified including 84 in the LDLR gene, 31 in APOB and 4 in PCSK9 gene. Twenty-eight variants were found in more than one individual and LDLR c.1448G > A (p. W483X) was most frequent one detected in 9 patients. Besides, we found 8 (7 LDLR and 1 APOB) novel variants referred as “pathogenic (or likely pathogenic) variants” according to in silico analysis. In the phenotype analysis, patients with LDLR null mutation had significantly higher LDL cholesterol level than LDLR defective and APOB/PCSK9 mutation carriers and those with no mutations (p < 0.001). Furthermore, 13 double heterozygotes, 16 compound heterozygotes and 5 true LDLR homozygotes were identified and the true LDLR homozygotes had the most severe phenotypes.ConclusionsThe present study confirmed the heterogeneity of FH genetics in the largest Chinese cohort, which could replenish the knowledge of mutation spectrum and contribute to early screening and disease management.

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Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred

Cited by 8 publications

References 21 publications

Autosomal recessive hypercholesterolemia in Spain

Autosomal recessive hypercholesterolemia in Spain

Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation

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