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

Autor: Roberto Monastero, Gabriella Misiano, Maurizio Averna, Davide Noto, V. Ingrassia, Antonina Pipitone, Vincenza Valenti, Angelo B. Cefalù, Rossella Spina, C. Scrimali, Carlo M. Barbagallo, Antonina Giammanco, Maria P. La Spada, Roberta Baschi
Přispěvatelé: Spina, R., Noto, D., Barbagallo, C., Monastero, R., Ingrassia, V., Valenti, V., Baschi, R., Pipitone, A., Giammanco, A., La Spada, M., Misiano, G., Scrimali, C., Cefalu', A., Averna, M.
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Settore MED/09 - Medicina Interna
Endocrinology
Diabetes and Metabolism
Familial hypercholesterolemia
030204 cardiovascular system & hematology
0302 clinical medicine
Child
N-Glycosyl Hydrolases
Sicily
Genetics
Aged
80 and over
education.field_of_study
Nutrition and Dietetics
Allele frequency
Homozygote
High-Throughput Nucleotide Sequencing
Autosomal recessive hypercholesterolemia
Middle Aged
Autosomal Recessive Hypercholesterolemia
Settore MED/26 - Neurologia
Female
Cardiology and Cardiovascular Medicine
Adult
Adolescent
Genotype
Population
Hypercholesterolemia
Biology
DNA sequencing
03 medical and health sciences
Young Adult
ARH1
Internal Medicine
medicine
Humans
Allele
education
Genotyping
Alleles
Adaptor Proteins
Signal Transducing
Aged
Heterozygous carrier
Sequence Analysis
DNA
medicine.disease
NGS-based gene panel
030104 developmental biology
Genetic epidemiology
Receptors
LDL
Zdroj: Journal of clinical lipidology. 12(1)
ISSN: 1933-2874
Popis: Background Autosomal recessive hypercholesterolemia (ARH) is a rare inherited lipid disorder. In Sardinia, differently from other world regions, the mutated allele frequency is high. It is caused by mutations in the low-density lipoprotein receptor adaptor protein 1 gene. Fourteen different mutations have been reported so far; in Sardinia, 2 alleles (ARH1 and ARH2) explain most of the cases. Four ARH patients, all carriers of the ARH1 mutation, have been identified in mainland Italy and 2 in Sicily. Objective The objectives of the study were to improve the molecular diagnosis of familial hypercholesterolemia (FH) and to estimate the frequency of the ARH1 allele in 2 free-living Sicilian populations. Methods We sequenced by targeted next-generation sequencing 20 genes related to low-density lipoprotein metabolism in 50 hypercholesterolemic subjects. Subjects from 2 free-living populations from Northern (Ventimiglia Heart Study, 848 individuals) and Southern Sicily (Zabut Zabut Aging Project, 1717 individuals) were genotyped for ARH1 allele. Results We identified 1 homozygous carrier of the ARH1 mutation among the 50 hypercholesterolemic outpatients. Population-based genotyping of ARH1 in 2565 subjects allowed the identification of 1 heterozygous carrier. The overall estimated allele frequency of ARH1 in Sicily was 0.0002 (0.02%). Conclusions The identification of a new case of ARH in Sicily among 50 clinically diagnosed FH highlights the importance of next-generation sequencing analysis as tool to improve the FH diagnosis. Our results also indicate that ARH1 carrier status is present in ∼1:2500 of Sicilian inhabitants, confirming that ARH is extremely rare outside Sardinia.
Databáze: OpenAIRE
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