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

Autor: Faina M. Zakharova, T. Yu. Komarova, M. Yu. Mandelshtam, N. A. Grudinina, A. S. Golovina, V. O. Konstantinov, M. P. Serebrenitskaya, Vadim B. Vasilyev, V. A. Korneva, B. M. Lipovetsky
Rok vydání: 2013
Předmět:
Zdroj: Russian Journal of Genetics. 49:673-676
ISSN: 1608-3369
1022-7954
DOI: 10.1134/s1022795413040066
Popis: Using an automated fluorescent single-strand conformation polymorphism (SSCP) analysis of the entire coding region, promoter zone, and exon-intron junctions of the low-density lipoprotein (LDL) receptor gene, we examined 80 DNA samples of patients with familial hypercholesterolemia (FH) from Petrozavodsk. We revealed mutations that might cause FH in five probands, including FH-North Karelia (c.925-931del7) mutation and four previously unknown mutations. These novel mutations included a transversion (c.618T>G (p.S206R), one nucleotide insertion c.195_196insT (p.FsV66:D129X), a complex gene rearrangement c.192del10/ins8 (p.FsS65:D129X), and a single nucleotide deletion c.2191delG (p.FsV731:V736X). Three out of four novel mutations produce an open reading frame shift and the premature termination of translation. An analysis of the cDNA sequence of the LDL receptor showed that this might result in the formation of a transmembrane-domain-deficient receptor that is unable to bind and internalize the ligand. Our results suggest the absence of a strong founder effect associated with FH in the Petrozavodsk population.
Databáze: OpenAIRE
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