2 research outputs found

    Genetic and Clinical Features of Shwachman-Diamond Syndrome in Russian Population: Prospective Study

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    Background. Shwachman-Diamond syndrome (SDS) is the rare genetic autosomal recessive disorder with pathogenic variants in SBDS gene. The spectrum of SBDS gene variants in patients with SDS and features of disease course have not been studied before in Russian population.Objective. The aim of the study was to describe all the variants of SBDS gene and clinical and laboratory abnormalities in children with SDS. Methods. In this prospective study exocrine pancreatic function was estimated by amylase and lipase activity in blood, steatorrhea presence and stool elastase levels during the initial hospitalization. Haematological disorders were analysed by complete blood count. Bone abnormalities were diagnosed via X-ray imaging. Growth delay was established due to anthropometry indicators and percentile curves. Molecular genetic testing was performed with using next generation sequencing and Senger sequencing.Results. Pathogenic variants in SBDS gene (8 in general) were revealed in 25 (89%) out of 28 children with SDS. The most common variant (in 23 patients, 82%) was с.258+2T>C, and in 18 cases it was in compound heterozygous state with c.183_184delTAinsCT. Two patients had с.653G>A (p.Arg218Gln) variant and for one patient for every of the following variants: c.258+1G>A, c.107delT, с.356G>A, c.297_300delAAGA, c.338C>T. All children with SDS had growth delay, in 11 (39%) cases we revealed bone abnormalities. In blood samples of 24 (86%) children we revealed neutropenia and less frequently anemia and thrombocytopenia. The stool elastase I decreased activity (< 200 pg/g) was revealed in 26 (92%) patients. 21 (75%) children had cytolysis syndrome.Conclusion. Pathogenic variants of SBDS gene were revealed in majority of Russian children with SDS. The most frequent are c.258+2T>C and c.183_184delTAinsCT variants. Clinical signs of Shwachman-Diamond syndrome manifest since birth with growth delay, steatorrhea and haematological disorders

    Ribosomal DNA Abundance in the Patient’s Genome as a Feasible Marker in Differential Diagnostics of Autism and Childhood-Onset Schizophrenia

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    Introduction: Differential diagnostics of early-onset schizophrenia and autism spectrum disorders (ASD) are a problem of child psychiatry. The prognosis and relevant treatment are to a large degree determined by the correctness of diagnosis. We found earlier that leucocyte DNA of adult schizophrenia patients contained significantly larger copy numbers of ribosomal repeats (rDNA) coding for rRNA, than DNA of mentally healthy controls. Aim: To compare the contents of ribosomal repeats in the leucocyte DNA of children with schizophrenia, children with ASD, and healthy age-matched controls to estimate the possibility of using this genetic trait in the differential diagnostics of the two types of disorders. Patients and methods: Blood samples of patients with infantile autism (A—F84.0 according to ICD-10, N = 75) and with childhood-onset schizophrenia (SZ—F20.8 according to ICD-10, N = 43) were obtained from the Child Psychiatry Department of the Mental Health Research Center. The healthy control blood samples (HC, N = 86) were taken from the Research Centre for Medical Genetics collection. The recruitment of cases was based on the clinical psychopathologic approach. DNA was extracted from blood leukocytes with organic solvents. Nonradioactive quantitative hybridization technique was applied for determining the abundance of ribosomal repeats in the genomes. Statistical processing was performed using StatPlus, Statgraphics and MedCalc. Findings: DNA derived from SZ cases contained 565 ± 163 rDNA copies, which is significantly (p < 10−6) higher than the rDNA content in ASD cases (405 ± 109 copies) and controls (403 ± 86 copies). The HC and A groups did not differ by rDNA copy number (p > 0.4). The genetic trait “rDNA copy number in patient’s genome” can potentially be applied as an additional marker in differential diagnostics of childhood-onset schizophrenia and autism spectrum disorders
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