RESUMEN
The search for two mutations, FH-Helsinki and FH-North Karelia, in LDL receptor gene was carried out in patients with familial hypercholesterolemia from St. Petersburg (80 families) and Petrozavodsk (80 families) using allele-specific PCR and analysis of single-stranded DNA fragment conformation polymorphism (SSCP analysis) with subsequent sequencing. The FH-North Karelia mutation was found in one family in St. Petersburg and in one family in Petrozavodsk, while FH-Helsinki mutation was not detected in any of the samples. Hence, the two "Finnish" mutations together responsible for 2/3 familial hypercholesterolemia cases in Finland were extremely rare in the Russian regions neighboring Finland.
Asunto(s)
Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo II/genética , Receptores de LDL/genética , Eliminación de Secuencia/genética , Finlandia/epidemiología , Humanos , Incidencia , Reacción en Cadena de la Polimerasa Multiplex , Polimorfismo Conformacional Retorcido-Simple , Federación de Rusia , Análisis de Secuencia de ADNRESUMEN
Novel mutation p. FsS65:D129X in human low density lipoprotein receptor gene in a female patient with typical clinical symptoms of familial hypercholesterolemia is described in this paper. Segregation of this mutation with hypercholesterolemia in the family of the patient from Petrozavodsk is demonstrated.
Asunto(s)
ADN/genética , Predisposición Genética a la Enfermedad , Hiperlipoproteinemia Tipo II/genética , Mutación , Receptores de LDL/genética , Femenino , Humanos , Hiperlipoproteinemia Tipo II/sangre , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Receptores de LDL/sangre , Estudios RetrospectivosRESUMEN
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.