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2010 | 51 | 1 |
Tytuł artykułu

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations

Treść / Zawartość
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Autosomal dominant hypercholesterolemia (ADH) is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, a molecular analysis of LDLR and APOB was performed in a group of 378 unrelated ADH patients, to explore the mutation spectrum that causes hypercholesterolemia in Poland. All patients were clinically diagnosed with ADH according to a uniform protocol and internationally accepted WHO criteria. Mutational analysis included all exons, exon-intron boundaries and the promoter sequence of the LDLR, and a fragment of exon 26 of APOB. Additionally, the MLPA technique was applied to detect rearrangements within LDLR. In total, 100 sequence variations were identified in 234 (62%) patients. Within LDLR, 40 novel and 59 previously described sequence variations were detected. Of the 99 LDLR sequence variations, 71 may be pathogenic mutations. The most frequent LDLR alteration was a point mutation p.G592E detected in 38 (10%) patients, followed by duplication of exons 4-8 found in 16 individuals (4.2%). Twenty-five cases (6.6%) demonstrated the p.R3527Q mutation of APOB. Our findings imply that major rearrangements of the LDLR gene as well as 2 point mutations (p.G592E in LDLR and p.R3527Q in APOB) are frequent causes of ADH in Poland. However, the heterogeneity of LDLR mutations detected in the studied group confirms the requirement for complex molecular studies of Polish ADH patients.
Wydawca
-
Rocznik
Tom
51
Numer
1
Opis fizyczny
p.95-106,ref.
Twórcy
autor
  • Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-210 Gdansk, Poland
autor
  • Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-210 Gdansk, Poland
autor
  • Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-210 Gdansk, Poland
autor
  • Department of Metabolic Diseases, Endocrinology and Diabetology, Children's Memorial Health Institute, Warsaw, Poland
  • Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland
autor
  • I Department of Cardiology, Medical University of Gdańsk, Poland
  • Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland
autor
  • Department of Metabolic Diseases, Endocrinology and Diabetology, Children's Memorial Health Institute, Warsaw, Poland
autor
  • Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland
autor
  • Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands
autor
  • I Department of Cardiology, Medical University of Gdańsk, Poland
autor
  • Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-210 Gdansk, Poland
Bibliografia
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Typ dokumentu
Bibliografia
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