[Familial hypercholesterolemia due to a new mutation in the low density lipoprotein receptor gene].

Familial hypercholesterolemia (FHC) is a genetic disorder manifest as a rise in serum cholesterol level responsible for the development ofcardiovascular diseases. To study genetic peculiarities of FHC in Kareliya. 109 patients of the 196 ones with FHC (124 families) were subjected to genetic examination. Other parameters studied included the lipid spectrum, blood glucose level, ECG, 24 hr ECG monitoring, echocardiography, triplex scanning of brachiocephalic arteries and lower limb vessels, functional tests. Simon Broom criteria were used to diagnose FHC. "Definitive" FHC was diagnosed in 136 (69.4%) patients, (probable) FHC in 30.6%. The total encoding region of the low density lipoprotein receptor gene was sequenced in 109 (55.6%) patients in parallel with the search for major mutations in the APOB and PCSK9 genes. A total of 13 mutations (p.G20R, c. 192del110/ins8, c.195-196insT, p.S206R, c925- 931del17, p.S447C, p.13981, p.L426P, L511S, c.1686del18/insT, p.L646I, p.N640N, c.2191delG) were identified in low density lipoprotein receptor gene; seven of them are reported for the first time in the world. No major mutations in the APOB and PCSK9 genes were found. The new c.2191delG (p.(Val73 1Serfs*6)) mutation is characterized and its segregation with familial dyslipidemia is shown. The present case is characterized by the absence of clinical picture of coronary heart disease and the family history complicated by cerebral basin lesion. Phenotypic manifestations of atherosclerosis in FHC with gene mutations need further studies.