Genetic Landscape of Nephropathic Cystinosis in Russian Children.

Nephropathic cystinosis is a rare autosomal recessive disorder characterized by amino acid cystine accumulation and caused by biallelic mutations in the CTNS gene. The analysis methods are as follows: tandem mass spectrometry to determine the cystine concentration in polymorphonuclear blood leukocytes, Sanger sequencing for the entire coding sequence and flanking intron regions of the CTNS gene, multiplex PCR to detect a common mutation-a 57 kb deletion, and multiplex ligation-dependent probe amplification to analyze the number of exon copies in the CTNS gene. Haplotype analysis of chromosomes with major mutations was carried out using microsatellite markers D17S831, D17S1798, D17S829, D17S1828, and D17S1876. In this study, we provide clinical, biochemical, and molecular genetic characteristics of 40 Russian patients with mutations in the CTNS gene, among whom 30 patients were selected from a high-risk group of 85 people as a result of selective screening, which was carried out through cystine concentration measurement in polymorphonuclear blood leukocytes. The most common pathogenic variant, as in most described studies to date, was the 57 kb deletion, which represented 25% of all affected alleles. Previously non-described variants represented 22.5% of alleles. The founder effect in the Karachay and Chechen ethnic groups was shown for the following major variants: c.1015G > A and c.518A > G.

[The polymorphic markers of АРОВ and APOE genes and the chromosomal region 3q21-q25 are associated with the development of diabetic nephropathy in type 1 diabetes mellitus].

Early studies of the association of a large group of gene candidates indicated that only the polymorphic markers of angiotensin-converting enzyme (ACE) I gene and endothelial vascular cell NO-synthetase (NOS3) gene were associated with diabetic nephropathy (DN) in type 1 diabetes mellitus. The purpose of this study was to examine DN predisposition in patients with type 1 DM, by using the polymorphic markers of the genes of apolipoproteins Е (АРОЕ) and В (АРОВ) which encode for lipid metabolic proteins, as well as polymorphic microsatellites in the chromosomal region 3q21-q25. Two groups of patients of patients with type 1 DM with (n = 54) and without (n = 65) DN were examined to analyze the gene association with DN. Analyzing the frequencies of the alleles and genotypes of the polymorphic marker E2/E3/E4 ofAPOR gene has indicated that the carriers of the allele E3 and the genotype E3/ E3 have a higher risk for DN (OR = 2.08 and 2.16, respectively). In case of АРОВ gene, the carriers of allele I and genotype II of the polymorphic marker I/D have been ascertained to have a higher risk for DN (OR = 1.91 and 2.11, respectively) while those of allele Dhave, on the contrary, a lower risk for DN (OR = 0.52). The authors have revealed an association of a group of polymorphic microsatellites with DN in the chromosomal region 3q21-q25. There is the greatest association for the marker D31550. The carriers of allele 12 (OR = 4.85) and genotype 12/14 (OR = 6.25) have a much higher risk for DN. In all probability, in the chromosomal region 3q21-q25, there is a major gene that initiates the development of DN whereas other genes associated with DN affect the rate of its progression to a greater extent. Thus, among the Moscow Russian dwellers suffering from type 1 DM, the progression of DN is mainly associated with the genes of ACE, NOS3, APOE, and АРОВ while the major gene that determines the first stages of DN development in type 1 DM is likely to be located in the chromosomal region 3q21-q25.