New mutations in low-density lipoprotein receptor gene in familial hypercholesterolemia patients from Petrozavodsk

Komarova, T. Yu.; Golovina, A. S.; Грудинина, Н. А.; Zakharova, F. M.; Korneva, Viktoria; Lipovetsky, B. M.; Serebrenitskaya, M.; Константинов, В. О.; Vasilyev, V. B.; Mandelshtam, M. Yu.

doi:10.1134/s1022795413040066

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…Most of these variants were unique but some LDLR variants occurred in several unrelated patients: p.Cys68Phe, p.Pro196Arg, p.Cys318Trp, p.Tyr375Asp and p.Ile566Phe. Of 35 variants previously described in the literature [ 6 , 7 , 8 , 9 , 10 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] only for the Russian population, six variants were also found in this study. Most of these variants were also unique, except for variant LDLR -p.Cys160Gly, that was found in six unrelated patients.…”

Section: Resultssupporting

confidence: 71%

“…The search strategy described above yielded 665 citations; 474 remained after duplicate removal. After the analysis of the abstracts referring to genetic testing or LDLR , APOB and PCSK9 variants in FH patients, 27 articles were selected, of which 25 contained data on the LDLR , APOB , and PCSK9 variants, including three of previously published articles by our group [ 6 , 7 , 8 , 9 , 10 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. These articles describe 91 causal variants of LDLR gene, one variant of APOB, and one variant of PCSK9 ( Figure 1 , Table A1 , Table A2 and Table A3 in Appendix A ).…”

Section: Resultsmentioning

confidence: 99%

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The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Мешков

Ершова

Киселева

et al. 2021

Genes

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Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.

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Section: Resultssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Мешков

Ершова

Киселева

et al. 2021

Genes

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“…The small size of the cohort studied may partly account for these differences. In our opinion, these results highlight the genetic peculiarity of the Russian population, with respect to the spectrum of LDLR gene mutations found in patients with FH (Komarova et al, 2013b;Korneva et al, 2017a).…”

Section: Ldlr Mutation Spectrum In Patients With Fh From Petrozavodsksupporting

confidence: 63%

Familial Hypercholesterolemia in Russia: Three Decades of Genetic Studies

et al. 2020

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The first studies of familial hypercholesterolemia (FH) in Russia go back to late 1980-ies. For more than 10 years the research in this field was carried out in Saint-Petersburg, the megapolis in the North-West Russia. Studies were focused on the search for causative mutations in low-density lipoprotein receptor gene (LDLR). Gradually the research was spread to Petrozavodsk in Karelia and in the XXI century two more centers contributed in investigations of genetics of FH, i.e., in Moscow and Novosibirsk. The best studied is the spectrum of mutations in LDLR, though genetic abnormalities in APOB and PCSK9 genes were also considered. Despite that some 40% mutations in LDLR found in Saint-Petersburg and Moscow are referred to as specific for Russian population, and this proportion is even higher in Karelia (ca. 70%), rapid introduction of NGS and intensifying genetic research all over the world result in continuous decrease of these numbers as “Slavic” mutations become documented in other countries. The samplings of genetically characterized patients in Russia were relatively small, which makes difficult to specify major mutations reflecting the national specificity of FH. Moreover, the majority of studies accomplished so far did not explore possible associations of certain mutations with ethnic origin of patients. By now the only exception is the study of Karelian population showing the absence of typical Finnish mutations in the region that borders on Finland. It can be concluded that the important primary research partly characterizing the mutation spectrum in FH patients both in the European and Siberian parts of Russia has been done. However, it seems likely that the most interesting and comprehensive genetic studies of FH in Russia, concerning various mutations in different genes and the variety of ethnic groups in this multi-national country, are still to be undertaken.

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“…Familial hypercholesterolemia (FH) (OMIM 143890) is an autosomal dominant inborn error of metabolism leading to high levels of low density lipoprotein (LDL) (OMIM 606945) due to decreased clearance via specific LDL-receptor (LDLR). The disease is common (1:500) and can be diagnosed by detection of mutations in LDLR gene (Komarova et al, 2013). The genetic basis of FH is a large array of mutations in the LDLR gene, resulting in a lack of functional receptors for LDL on the liver cell surface, giving rise to increased plasma LDL levels (Alharbi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Screening for genetic mutations in LDLR gene with familial hypercholesterolemia patients in the Saudi population

et al. 2015

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Familial hypercholesterolemia (FH) is caused by genetic defects involving the low density lipoprotein-receptor (LDL-R), predisposing affected people to premature atherosclerotic cardiovascular disease and death. The aim of the present study was to assess certain exons in the LDLR gene mutation detection analysis affecting in the Saudi population with FH. This case-control study was carried out with 200 subjects; 100 were FH cases and 100 were healthy controls. Five mL of venous blood samples were collected from all the subjects and used for biochemical and genetic analysis. DNA was extracted from 2 mL of the EDTA samples, and precise primers were designed for LDL-R gene which includes Exon 3, 4 and 8. PCR was followed by DNA sequencing. In our study, we found 25 mutations in cases in Exon-3 and 2 mutations in controls, however, we have found only 5 mutations in exon 4 and none of the mutations were identified in exon 8. We conclude that screening of FH among Saudi population is very important to identify individuals who are prone to develop the disease.

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New mutations in low-density lipoprotein receptor gene in familial hypercholesterolemia patients from Petrozavodsk

Cited by 6 publications

References 19 publications

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Familial Hypercholesterolemia in Russia: Three Decades of Genetic Studies

Screening for genetic mutations in LDLR gene with familial hypercholesterolemia patients in the Saudi population

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