Molecular characterization of familial hypercholesterolemia in Spain

Palacios, Lourdes; Grandoso, Laura; Cuevas, N; Olano-Martín, Estíbaliz; Martı́nez, Antonio; Tejedor, Diego; Stef, Marianne

doi:10.1016/j.atherosclerosis.2011.12.021

Cited by 111 publications

(72 citation statements)

References 28 publications

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“…38 Over 400 different FH-causing mutations have been described in the Spanish population, almost all of which have been described in other populations and none accounting for >6.5% of cases. 4 In fact, our presently obtained prevalence value is similar to the rates obtained using genetic criteria. 21 This reinforces the idea that the classical clinical criteria identify only the most severe cases.…”

Section: Discussionsupporting

confidence: 86%

“…When no mutation was identified, complete sequencing was conducted of the LDLR promoter, exons, and intron-exon boundaries, as well as the APOB LDLR-binding domain. 4,25 From 2012 to 2015, molecular diagnosis was performed using next-generation sequencing of the LDLR promoter, exons, and intron-exon boundaries; the APOB LDLR-binding domain; the PCSK9 promoter, exons, and intron-exon boundaries; and the LDLRAP1 promoter, exons, and intron-exon boundaries. 24 From all analyzed studies, we selected the patients carrying at least 2 mutations within the 3 genes responsible for FH or in LDLRAP1, as previously described.…”

Section: Molecular Diagnosismentioning

confidence: 99%

“…1 Homozygous FH (HoFH) is caused by mutations in both copies of any of the 3 main genes involved in FH development: LDL receptor (LDLR; 95% of cases; OMIM #606945); 1 apolipoprotein B (APOB; 2% to 5% of cases; OMIM #107730); 2 and proprotein convertase subtilisin/kexin type 9 (PCSK9; <1% of cases; OMIM #607786). 3,4 Additionally, recessive autosomal FH has been described, involving mutations on both LDLRAP1 alleles (<1% of cases; OMIM #695747). 5 The recessive form of FH is clinically indistinguishable from HoFH, [6][7][8] although less aggressive phenotypes have also been described, 9 for this reason, this form of FH has also been included in our studies.…”

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confidence: 99%

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Homozygous Familial Hypercholesterolemia in Spain

Sánchez-Hernández¹,

Civeira²,

Stef³

et al. 2016

Circ Cardiovasc Genet

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Recent genetic studies of FH highlight the great variability of the clinical phenotypes in HoFH and heterozygous FH (HeFH), the poor genotype-phenotype correlation, and the large clinical overlap between HoFH and HeFH. 15,[18][19][20] These findings can be explained based on the variations in the number of genes involved, the specific pathogenic mutations, and Background-Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1

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Section: Discussionsupporting

confidence: 86%

Section: Molecular Diagnosismentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Homozygous Familial Hypercholesterolemia in Spain

Sánchez-Hernández¹,

Civeira²,

Stef³

et al. 2016

Circ Cardiovasc Genet

Self Cite

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“…In addition, the range of plasma LDL cholesterol levels in FH overlaps with that of people with non-genetic polygenic hypercholesterolemia. 12,25) On the other hand, tendon xanthomas are strongly associated with a genetic diagnosis and highly specific for FH patients. 12) Achilles tendon xanthomas in particular have been used as one of the criteria for the clinical diagnosis of FH in JAS and the Simon Broome Register because of their high sensitivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

Estimated Prevalence of Heterozygous Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome

et al. 2017

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SummaryHeterozygous familial hypercholesterolemia (FH) represents a strong risk for development of premature coronary artery disease (CAD). However, the majority of patients with FH are undiagnosed and the prevalence likely represents an underestimate in most countries. In Japan, the possible contribution of FH to the development of CAD may be higher because of the low incidence of CAD among the general population. We estimated the prevalence of heterozygous FH by measuring Achilles tendon thickness (ATT) in patients with acute coronary syndrome (ACS).A total of 359 patients suffering from ACS were enrolled in this multicenter registration study. Heterozygous FH was defined according to the diagnostic criteria proposed by the Japan Atherosclerosis Society. After excluding 63 patients because of missing ATT data or plasma triglyceride levels that were 4.5 mmol/L or more, 296 patients were eligible for inclusion in the study. The number of patients with ATT of 9 mm or more was 53 (17.9%). They were significantly younger and had significantly higher LDL cholesterol levels than patients with an ATT less than 9 mm. The prevalence of heterozygous FH was 5.7% (1/17.5) and more prominent in younger patients who were less than 60 years old (7.8%). In patients with ATT of 9 mm or more, approximately 1 in 3.5 fulfilled the criteria for heterozygous FH.We demonstrated the usefulness of measuring ATT by radiography and the high prevalence of heterozygous FH in patients with ACS in Japan, especially in younger patients who were less than 60 years old. (Int Heart J 2017; 58: 88-94)

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“…Thus, all epidemiological, cross-sectional, cohort, retrospective, longitudinal, observational, comparative, case-control, and case reports were considered containing the following keywords or MeSH terms: familial hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, type II hyperlipoproteinemia, LDL receptor mutation, apoB mutation, PCSK9 mutation, xanthomas, arcus senilis, aortic valvular lesions and most frequent FH mutations encountered in Latin America are on LDLR . However, autosomal recessive FH and APOB mutations have also been reported in this region (55)(56)(57)(58).…”

Section: Methodsmentioning

confidence: 99%

The panorama of familial hypercholesterolemia in Latin America: a systematic review

Mehta

Zubirán

Martagón

et al. 2016

Journal of Lipid Research

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penetrance. Autosomal dominant FH is attributed to mutations in three different genes: LDL receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) (1,(3)(4)(5). Other FH genes have been searched for using exome sequencing without success (2). FH caused by mutations in LDLR adaptor protein (LDLRAP) is known as autosomal recessive FH (2). FH is the most common monogenic disorder leading to premature CHD; despite this fact, it is notoriously underdiagnosed and undertreated worldwide (6).Homozygous FH (HoFH) is characterized by extremely high levels of LDL-C (460-1,160 mg/dl) and early onset coronary artery disease (typically by the second decade of life) (7). Mean LDL-C concentration in untreated patients is close to 615 mg/dl (7,8). Patients are classified into two groups based on the level of LDLR activity, either <2% (receptor negative) or 2-25% (receptor defective). Receptor defective patients have a better prognosis than receptor negative cases (9-11).Heterozygous FH (HeFH) is caused by a single inherited copy of a mutation. The frequency of a heterozygous mutation is >90, 5, and <1% in the LDLR, APOB, and PCSK9 genes, respectively (5). A causal mutation in one of these genes is identified in 60-80% of cases. Affected individuals are characterized by LDL-C levels two to three times greater than normal (190-400 mg/dl). The mean untreated LDL-C concentration is 199.9 mg/dl (12). HeFH is suspected

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Molecular characterization of familial hypercholesterolemia in Spain

Cited by 111 publications

References 28 publications

Homozygous Familial Hypercholesterolemia in Spain

Homozygous Familial Hypercholesterolemia in Spain

Estimated Prevalence of Heterozygous Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome

The panorama of familial hypercholesterolemia in Latin America: a systematic review

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