👤 Masha Kolesnikova

To describe the phenotype of CLN-associated retinal dystrophy in a subset of patients at the Columbia University Medical Center, United States, and the Hospital das Clínicas de Pernambuco, Brazil, in comparison to the published literature. Eleven patients with confirmed biallelic variants in the CLN genes were evaluated via dilated fundus examination, clinical imaging, and full-field electroretinogram. A thorough literature search was conducted to determine previously published variants and associated phenotypes. Genetic testing confirmed the presence of variants in CLN3, CLN7/MFSD8, CLN8, and GRN/CLN11. Five novel variants were identified, and four novel phenotypes of previously published alleles were described. The phenotype differed among patients with variants in the same gene and sometimes among patients with the same allele. Substantial phenotypic variability among variants in the CLN genes makes identification of genotype-phenotype or allele-phenotype correlations challenging. Further study is required to establish an extensive database for adequate patient counseling. Show less

The aim of this cross-sectional observational study is to determine the contribution of polymorphisms of energy metabolism genes into metabolic disorders in Russian and Buryat adolescents with overweight and obesity. The study included 354 Russian and Buryat adolescents aged 13-18 years. Body mass index and serum levels of glucose, insulin, and leptin were measured and insulin resistance index HOMA-IR was calculated. Molecular genetic analysis for the presence of 9 loci of energy metabolism genes LEP, LEPR, POMC, FTO, and MC4R were analyzed. It was found that the risk of metabolic disorders is associated with the presence of polymorphic loci of leptin receptor gene LEPR and melanocortin receptor gene MC4R (LEPR rs1137100+LEPR rs1137101 and LEPR rs1137100+MC4R rs17782313) in Russian adolescents with overweight and obesity and polymorphisms of the gene FTO (FTO rs9939609+rs8050136) associated with fat mass and obesity in Buryat adolescents. Show less

Predictive models of comorbidity, dyslipidemic disorders and essential arterial hypertension, in Russian adolescents aged 12 to 18 years (mean 15.48±1.53) were formulated with consideration for biochemical (lipid profiles) and genetic parameters (carrier state of gene polymorphic variants of apolipoprotein genes ApoA1 (-75G/A and +83C/T), ApoB (Ins/Del), ApoC3 (S1/S2), and ApoE (ε2/ε3/ε4). Significant prognostic risk factors for the mentioned comorbid pathologies were lipid metabolism parameters HDL-Ch, LDL-Ch, VLDL-Ch and carrier state of the +83T allele of the ApoA1 gene and Del allele of the ApoB gene. The obtained mathematical model is characterized by high predictive accuracy: the percentage of correct classification or the rate of correct assignment of each participant to the proper group was 96.33%. Show less

Using MDR bioinformatic analysis we studied gene-gene interactions between apolipoprotein genes in adolescents with essential arterial hypertension and dyslipidemia against the background of essential arterial hypertension. Optimal models of gene-gene interactions were formed. The six-locus model was the most significant: (ApoA1(+83T), ApoA1(-75A), ApoB(Del), ApoC3(S2), ApoE(ε2), ApoE(ε4). The maximum synergism in both adolescent groups were shown for allele variants ApoA1(-75A), ApoB(Del), and ApoE(ε4). The maximum contribution to gene-gene interactions entropy was made by allelic polymorphisms ApoA1(-75A) and ApoE(ε4) and (in the comorbid pathology group) for ApoE(ε4)+ApoB(Del). Show less