High-performance sequencing in the diagnosis of monogenic diseases: Possibilities and limitations

The paper deals with the topical issues of using high-performance sequencing to diagnose monogenic diseases. The de facto method is widely used in clinical practice. The rapid development of high-performance sequencing requires that medical geneticists and pediatricians specializing in hereditary diseases should understand its possibilities and limitations, choose a strategy for diagnosis in each specific patient, and competently interpret the obtained results

Gender characteristics of the clinical manifestations of cardiovascular system involvement in X-linked Alport syndrome

The paper describes a clinical case of a family, in which its 5 members (4 women and 1 man) were found to have the new missence mutation c. 3098G>A, p.(1033D) in the gene encoding the α5-chain of type IV collagen (COL4A5) responsible for the development of X-linked Alport syndrome. At the same time, all the four female carriers were observed to have had kidney injury since infancy (at the age of 3 years), an age progressive glomerular filtration rate reduction to 78 ml/min; proteinuria up to 2 g/day; hypertension, and aortic dilatation (at the level of the ring, sinuses, and ascending aorta). In this family, one man aged 33 years had died from renal failure (DNA diagnosis was not made). The second 26-year-old man with the documented mutation in the clinical picture had proteinuria up to 2.5 g/l, persistent hematuria up to 100 red blood cells in the field of vision; a glomerular filtration rate decrease to 50 ml/min; sensorineural deafness, and cardiovascular abnormalities (dilatation of the left ventricle, ring, sinuses, and ascending aorta; aortic regurgitation, 2 cm; and stable hypertension)

The first results of tuberous sclerosis registry

The purpose of establishing and maintaining a tuberous sclerosis registry is to collect data on the clinical manifestations and outcomes of the disease, and drug and non-drug interventions. The registry includes data on 303 people (156 men and 147 women) aged 4 months to 28 years who are diagnosed as having this disease. Most patients are the residents of Moscow and its Region (102/303; 33,6%). Thirty (9,9%) of the 303 patients are registered to have a family history of tuberous sclerosis. TSC1 and TSC2 gene mutations are detected in 29 (38,6%) and 46 (61,4%) patients, respectively. The TSC2 gene mutations previously undescribed in the world literature are found in 10 patients. There is epilepsy in 86,8% (263/303), intellectual developmental disorders in 39,3% (119/303), subependymal giant cell astrocytomas in 16,2% (49/303), tubers in 61% (81/131), subependymal nodules in 65,7% (86/131), hypopigmentation spots in 66,3% (201/303), facial angtofibromas in 29,4% (89/303), cardiac rhabdomyomas in 44,2% (134/303), and renal angiomyolipomas in 41,6% (126/303). West's syndrome is noted in 68 (25,9%) of the 262 epileptic patients; symptomatic focal epilepsy is seen in 149 (56,9%) patients. Seven patients took everolimus for subependymal giant cell astrocytomas. The registry demonstrates the late diagnosis of tuberous sclerosis, the limitation of genetic testing, and physicians' inadequate attention to the psychiatric manifestations of the disease

[Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer's disease patients and in normal cohorts from Russian populations].

Three genes mutations in which cause familial forms of Alzheimer's disease are known to date:PSEN1, PSEN2 and APP; and APOE gene polymorphism is a strong risk factor for Alzheimer's disease. We have evaluated allele and genotype frequency distribution of rs11136000 polymorphism in clusterin (CLU) gene (or apolipoprotein J, APOJ) in populations of three Russian regions and i nAlzheimhner's diseasepatients. Genome-wideassociation studies in samples from several European populations have recently revealed highly significant association o fCLU gene with AD (p = 8.5 x 10(-10)). We found no differences in allele and genotype frequencies of rs11136000 between populations from Moscow, Ural and Siberia regions. The allele frequencies are close to those in European populations. The genetic association analysis in cohort of Alzheimer's disease patients and normal individuals (>500 individuals ineach group) revealed no significant association of the rs11136000 polymorphism in CLU with Alzheimer's disease in Russian populations. Although our resultsdo not confirm the role of CLU gene as a majorgenetic factor forcommon form of Alzheimer's disease, the data do not rule out the possibility of modest effect of CLU and interaction between CLU and APOE genotypes in etiology of Alzheimer's disease