Limited mutational heterogeneity in the LDLR gene in familial hypercholesterolemia in Tunisia

Jelassi, Awatef; Jguirim, Imen; Najah, Mohamed; Abid, A.; Boughamoura, Lamia; Maatouk, Fethi; Rouis, Mustapha; Boileau, Cathérine; Rabès, Jean-Pierre; Slimane, Mohamed Naceur; Varret, Mathilde

doi:10.1016/j.atherosclerosis.2008.07.011

Cited by 17 publications

(7 citation statements)

References 30 publications

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“…It is well known that high-frequency LDLR gene mutations can aid in the screening for FH. For example, the S472RfsX44 mutation (in exon 10) is responsible for approximately 42% of the patients with FH in Tunisia 46 . The nine most common mutations have been shown to be responsible for 66.5% of the patients with FH in the Netherlands 23 .…”

Section: Discussionmentioning

confidence: 99%

The distribution and characteristics of LDL receptor mutations in China: A systematic review

Jiang

Sun

Dai

et al. 2015

Sci Rep

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Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene. This study aimed to perform a systematic review of LDLR mutations in China. Using PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure (Chinese), and the Chinese Biological and Medical database (Chinese), public data were limited to December 2014. The Medical Subject Headings terms and the following key words were used: “familial hypercholesterolemia”, “Chinese”, “China”, “Hong Kong”, and “Taiwan”. A total of 74 studies including 295 probands with 131 LDLR mutations were identified. Most of the mutations were located in exon 4 of LDLR and approximately 60% of the mutations were missense mutations. Thirty new mutations that were not recorded in the LDLR databases were found. In silico analysis revealed that most of the mutations were pathogenic. The primary LDLR mutations were C308Y, H562Y, and A606T, and all of the mutations had functional significance. Prevalence data suggest that there are nearly 3.8 million FH patients in China, although reported numbers are much smaller, suggesting that FH is widely misunderstood. This systematic review provides information that is specific to China for inclusion in the international FH database.

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Section: Discussionmentioning

confidence: 99%

The distribution and characteristics of LDL receptor mutations in China: A systematic review

Jiang

Sun

Dai

et al. 2015

Sci Rep

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“…We identified a heterozygous genetic variant in the MYH7 (p.Arg719Trp) gene and a missense heterozygous mutation in the LDLR (p.Gly343Cys) gene ( Figure 2 B), both classified as pathogenic in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria [ 14 ]. Indeed, these two mutations are already described as responsible for HCM and HeFH, respectively [ 15 , 16 ].…”

Section: Case Reportmentioning

confidence: 99%

Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection

et al. 2021

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Hypertrophic cardiomyopathy (HCM) and heterozygous familial hypercholesterolemia (HeFH), two of the most common genetic cardiovascular disorders, can lead to sudden cardiac death. These conditions could be complicated by concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as in the case herein described. A young amateur soccer player died in late October 2020 after a fatal arrhythmia and the autopsy revealed the presence of HCM with diffuse non-obstructive coronary disease. The molecular autopsy revealed a compound condition with a first mutation in the MYH7 gene (p.Arg719Trp) and a second mutation in the LDLR gene (p.Gly343Cys): both have already been described as associated with HCM and HeFH, respectively. In addition, molecular analyses showed the presence of SARS-CoV-2 lineage B.1.1.7 (UK variant with high titer in the myocardium. Co-segregation analysis within the family (n = 19) showed that heterozygous LDLR mutation was maternally inherited, while the heterozygous MYH7 genetic lesion was de novo. All family member carriers of the LDLR mutation (n = 13) had systematic higher LDL plasma concentrations and positive records of cardiac and vascular ischemic events at young age. Considering that HCM mutations are in themselves involved in the predisposition to malignant arrhythmogenicity and HeFH could cause higher risk of cardiac complications in SARS-CoV-2 infection, this case could represent an example of a potential SARS-CoV-2 infection role in triggering or unmasking inherited cardiovascular disease, whose combination might represent the cause of fatal arrhythmia at such a young age. Additionally, it can provide clues in dating the presence of the SARS-CoV-2 lineage B.1.1.7 in Northern Italy in the early phases of the second pandemic wave.

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“…The mutation p.Ser493ArgfsX44 in exon 10 appears to be the most frequent mutation. [11, 24, 30, 63, 64]. …”

Section: Molecular Defaults That Cause Adh In Tunisiamentioning

confidence: 99%

Autosomal Dominant Hypercholesterolemia: Needs for Early Diagnosis and Cascade Screening in the Tunisian Population

Jelassi¹,

Najah²,

Slimani³

et al. 2013

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Autosomal dominant hypercholesterolemia (ADH) is characterized by an isolated elevation of plasmatic low-density lipoprotein (LDL), which predisposes to premature coronary artery disease (CAD) and early death. ADH is largely due to mutations in the low-density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), or the proprotein convertase subtilisin/kexin type 9 (PCSK9). Early diagnosis and initiation of treatment can modify the disease progression and its outcomes. Therefore, cascade screening protocol with a combination of plasmatic lipid measurements and DNA testing is used to identify relatives of index cases with a clinical diagnosis of ADH. In Tunisia, an attenuated phenotypic expression of ADH was previously reported, indicating that the establishment of a special screening protocol is necessary for this population.

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Limited mutational heterogeneity in the LDLR gene in familial hypercholesterolemia in Tunisia

Cited by 17 publications

References 30 publications

The distribution and characteristics of LDL receptor mutations in China: A systematic review

The distribution and characteristics of LDL receptor mutations in China: A systematic review

Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (MYH7, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (LDLR, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection

Autosomal Dominant Hypercholesterolemia: Needs for Early Diagnosis and Cascade Screening in the Tunisian Population

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