Gaucher's disease

The article presents a rare clinical case of Gaucher's disease, a hereditary disease that belongs to lysosomal accumulation diseases. A 36-year-old patient was admitted to the clinic with complaints of pain in the left half of the abdomen, pain in the chest, cough with yellow sputum, difficulty breathing due to pain, general weakness. The mental underdevelopment, hepatosplenomegaly, anemia, thrombocytopenia, and the threat of rupture of the spleen were revealed in the process of collecting anamnesis and examination. The patient was transferred to the surgical department, and a splenectomy was performed. Histological examination of the spleen and genetic examination confirmed the diagnosis of Gaucher's disease.

First Results from the Prospective German Registry for Childhood Glaucoma: Phenotype–Genotype Association

Childhood glaucoma is a heterogeneous disease and can be associated with various genetic alterations. The aim of this study was to report first results of the phenotype–genotype relationship in a German childhood glaucoma cohort. Forty-nine eyes of 29 children diagnosed with childhood glaucoma were prospectively included in the registry. Besides medical history, non-genetic risk factor anamnesis and examination results, genetic examination report was obtained (23 cases). DNA from peripheral blood or buccal swab was used for molecular genetic analysis using a specific glaucoma gene panel. Primary endpoint was the distribution of causative genetic mutations and associated disorders. Median age was 1.8 (IQR 0.6; 3.8) years, 64% participants were female. Secondary childhood glaucoma (55%) was more common than primary childhood glaucoma (41%). In 14%, parental consanguinity was indicated. A mutation was found in all these cases, which makes consanguinity an important risk factor for genetic causes in childhood glaucoma. CYP1B1 (30%) and TEK (10%) mutations were found in primary childhood glaucoma patients. In secondary childhood glaucoma cases, alterations in CYP1B1 (25%), SOX11 (13%), FOXC1 (13%), GJA8 (13%) and LTBP2 (13%) were detected. Congenital cataract was associated with variants in FYCO1 and CRYBB3 (25% each), and one case of primary megalocornea with a CHRDL1 aberration. Novel variants of causative genetic mutations were found. Distribution of childhood glaucoma types and causative genes was comparable to previous investigated cohorts. This is the first prospective study using standardized forms to determine phenotypes and non-genetic factors in childhood glaucoma with the aim to evaluate their association with genotypes in childhood glaucoma.

Identification of a VHL gene mutation in atypical Von Hippel-Lindau syndrome: genotype–phenotype correlation and gene therapy perspective

Background Classical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both. Methods In this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome. Results We reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy. Conclusions Combined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.

Investigation of Genetic Alterations in Congenital Heart Diseases in Prenatal Period

The prenatal diagnosis of congenital heart disease (CHD) is important because of mortality risk. The onset of CHD varies, and depending on the malformation type, the risk of aneuploidy is changed. To identify possible genetic alterations in CHD, G-banding, chromosomal microarray or if needed DNA mutation analysis and direct sequence analysis should be planned.In present study, to identify genetic alterations, cell culture, karyotype analysis, and single nucleotide polymorphism, array analyses were conducted on a total 950 samples. Interventional prenatal genetic examination was performed on 23 (2, 4%, 23/950) fetal CHD cases. Chromosomal abnormalities were detected in 5 out of 23 cases (21, 7%). Detected chromosomal abnormalities were 10q23.2 deletion, trisomy 18, 8p22.3-p23.2 deletion, 8q21.3-q24.3 duplication, 11q24.2q24.5 (9 Mb) deletion, and 8p22p12 (16.8 Mb) deletion. Our study highlights the importance of genetic testing in CHD.

Bioinformatic analysis of genomes of commercial breeds of domestic pigs for identification of breed-specific SNPs

Determining the purebredity of farm animals in a breeding system is of key importance for the entire livestock industry. Purebred breeding of plant breeds is designed to ensure the production of high-value improving breeding material for commercial livestock breeding. Determination of purebredity of pigs can be carried out using single nucleotide polymorphisms (SNP). The multiplexing technology today has reached a level that makes it possible to characterize tens and hundreds of thousands of polymorphic variants simultaneously for hundreds of animals in one run of the device. For the first time, using bioinformatics methods, an analysis of genome-wide projects was carried out for 264 individuals of the species Sus scrofa located in the Sequence Read Archive (NCBI-SRA). The in silico genotype was determined for 692 SNPs, of which 59 SNPs showed a significant potential for differentiation of four commercial breeds: large white (the most significant SNPs are Chr. 6: g.85845403T> G and Chr.16: g.74053569T> C), duroc (Chr. 4: g.55661608A> G, Chr. 14: g.107689091T> C and Chr. 14: g.107939105T> C), landrace (Chr. 5: g.99925204A> G, Chr. 18: g .40100481A> G and Chr. 18: g.7664624A> G) and pietrain (Chr. 13: g.136017764T> C and Chr.17: g.47595840A> G). For breeds of duroc and pietrain pigs, the accuracy of differentiation was at least 99%, for breeds of large white and landrace pigs - over 80%, however, the sensitivity indicator characterizing the percentage of false positive results of classification was slightly over 65%. Creation of models for molecularand-genetic studies of these breeds will allow for a genetic examination of their purebredity, which will contribute to an increase in their breeding value and preservation of the national gene pool.

Strong Population Genetic Structure and Cryptic Diversity in the Florida Bonneted Bat (Eumops Floridanus)

Knowledge of genetic structure is essential for the long-term management and conservation of endangered species. We report the results from a genetic examination of the federally endangered Florida bonneted bat (Eumops floridanus) sampled from its range in southern Florida, USA. Bonneted bats are primarily found in four regions separated by approximately 100 to 250 kms, including three western natural areas (BW, PC, and CC) and one urban population on the east coast [Miami-Dade County (MD)]. We used 22 microsatellite loci and cytochrome b sequences to assess the extent of connectivity and levels of genetic diversity. Regional populations were highly differentiated (FST = 0.178) and model-based and multivariate analyses showed that MD was the most distinct among pairwise comparisons. Regional populations are small (i.e., Ne < 100) but demographically stable. Estimates of contemporary migration and historic gene flow suggest that regional populations do not frequently exchange migrants, but simulations suggest that the divergence among western regions is likely a result of recent genetic drift rather than long-term isolation. Significantly, mitochondrial DNA revealed that haplotypes from MD were similar or shared with those recognized as Eumops ferox from Cuba and Jamaica, and divergent (1.5%) from the remainder of bonneted bats in Florida. Our data support the management of each of the four populations as distinct population segments, and that BW, PC and CC combined are on an independent evolutionary trajectory from bats in MD. Critically, bonneted bats in Florida appear to harbor cryptic diversity that will require a reassessment of their taxonomy.

Peculiarities of feminizing surgical correction in children with disorders of sexual development

Purpose – to analyze own results of surgical treatment of serious forms of disorders of sexual development (DSD) in children after feminizing surgeries. To define practical protocol guides on the choice of the type of surgical correction. Materials and methods. Over the past 5 years surgeons of Lviv regional paediatric clinical hospital «OHMATDYT» have examined 12 children with DSD, signs of hermaphroditism (intersex). After complex examination the following states were diagnosed: androgenital syndrome in 5 girls (referred for further treatment to Kyiv paediatric medical centres); true hermaphroditism – 1 child; mixed gonadal dysgenesis (MCG) – 3 children; female pseudohermaphroditism (without determining genesis) – 1 child; partial testicular feminization syndrome, Morris syndrome (male pseudohermaphroditism) – 2 children. In connection with marked masculinization of external genitalia two children with MCG and the girl with pseudohermaphroditism underwent feminizing surgery, namely genital zone reconstruction, mobilization and excision of urogenital sinus walls, excision of genital cavernous bodies (in children with MCG) with clitoroplasty, vulvoplasty with labioplasty and vaginoplasty. Children with Morris syndrome are being prepared to feminizing surgery. Results. Each child had a personal examination plan. Verification of a child’s state lasted from several weeks to 2–3 months. Children who underwent feminizing surgery did not have male structures and had relatively well-developed female structures. More «natural», less traumatizing correction was preformed for each specific case. In all children who underwent surgery vagina opened into urogenital sinus lower than external urethral sphincter, so there was no need to form front vagina wall (back and side walls were formed). Out of all children treated in our hospital gender was legally changed to the opposite. Conclusions. The birth of a child with DSD is a most challenging problem for parents, doctors, psychologists and social workers. Such states require complex examination. Children with severe hypospadias must undergo genetic examination. Statistic data and our own experience show higher frequency of feminizing surgeries in such cases. The most difficult part of such surgeries proves to be the excision of genital cavernous bodies with clitoroplasty and clitoris translocation; the most responsible part in functional sense is vaginoplasty. Surgical treatment is not the final stage of treatment for such patients. Children with DSD require constant further dynamic checkups by gynaecologists, urologists, oncologists, endocrinologists, psychologists with relevant therapy correction. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: disorders of sexual development (DSD), hermaphroditism, feminizing correction.

Conducting forensic and genetic examination in civil judiciary as an object of constitutional protection

The article is devoted to the study of forensic genetic examination in civil proceedings as an object of constitutional protection, due to the emergence of the concept of forensic examination in general and forensic genetic examination, entities entitled to conduct forensic examinations, analyzing the legal basis of court - genetic examination in Ukraine. Characteristics of the legal basis for recognition of paternity/mother and establishing the fact of paternity/mother are presented. The admissible and appropriate evidence bases in such cases and the place of forensic genetic examination in in the system of evidence that can be involved in the case have been clarified. The features of this examination have been studied, basis to proceed with the molecular genetic examination, the grounds for conducting a molecular genetic examination have been determined, and the issues raised before the expert carrying out the expert research have been singled out. The analysis of judicial practice of consideration of cases on recognition of paternity/maternity and the establishment of the fact of paternity/maternity which is carried out with carrying out forensic genetic examination was carried out. The article analyzes the problematic issues that arise in the process of legal regulation of forensic genetic examination and the practice of applying legislation in this area. The problems of evasion of a party from participation in forensic genetic examination, namely, non-appearance at a certain time to participate in the examination, failure to provide materials for expert research and the legal consequences of such evasion for all participants in the case. This article offers ways to solve problematic aspects of the research. The conclusions on the application by the courts of the results of forensic genetic examination during the consideration of cases on recognition of paternity/maternity, establishment of the fact of paternity/maternity were generalized and made. Forensic genetic examination is an individual identify. This type of examination allows not only to categorically exclude paternity, but also to carry out the origin of the child from both parents due to blood relationship (identification), as well as the diagnosis of hereditary diseases in the fetus in the early stages of pregnancy. Conducting such an examination is an effective mechanism of constitutional protection, because the facts established as a result of the examination form the basis of the evidence base are considered in conjunction with other evidence available in the case file.

MO056KARYOMEGALIC INTERSTITIAL NEPHRITIS: AN ENTITY ASSOCIATED WITH DIFFERENT GENETIC MUTATIONS

Background and Aims Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic interstitial nephritis, The disease manifests as a slowly progressive chronic kidney disease and it is an underdiagnosed cause of interstitial nephritis. The presence of karyomegalic tubular epithelial cells in a renal biopsy specimen is the primary marker that makes KIN distinguishable from other common causes of chronic tubulointerstitial nephritis. KIN has recently been associated with the FAN1 (FANCD2 / FANCI-Associated nuclease 1) gene involved in DNA repair. In this article, we present two cases with KIN with different genetic associations. Methods Clinical, laboratory, and kidney biopsy finding along with genetic examination is presented. Results The first case was a 42-year-old male, who was diagnosed with gout eight years ago and renal dysfunction was found in routine examinations. He was admitted to the nephrology clinic with pain in both feet and legs for the last six months. He had a history of frequent upper respiratory tract infections in his childhood. There was no family member with kidney disease. There was a ten pack/year smoking history. He did not use alcohol, nephrotoxic drugs, or herbal substances. Physical examination was unremarkable. On admission, serum creatinine was 2.71 mg/ dl and the estimated glomerular filtration rate (e-GFR) was 28 ml/min/1.73m2. Liver function tests, Hepatitis B, C, and HIV serologies, and serum complement levels were normal. Urinalysis, including microscopic examination, did not reveal any abnormality. In 24-hour collected urine, 182 mg proteinuria was detected. Kidney biopsy revealed the following findings; mild tubular atrophy, nucleomegaly in tubular epithelial nuclei, rare multinucleation, and prominence in nuclei. There were no immune deposits present in immunofluorescence microscopy. A pathological diagnosis of KIN was made. In the genetic analysis, we detected c.358T&gt;C (p.Cys120Arg) mutation in UMOD gene by using clinical exome sequencing. According to the Human Gene Mutation Database (HGMD) guideline, this variant is assessed as likely pathogenic. There was no mutation in the FAN1 gene. The second case was a 64-year-old female, she had hypertension for eight years, and was referred to the nephrology clinic due to renal dysfunction. There was a history of pharyngitis four times a year. There was no history of smoking and alcohol use. She had been suffering from nocturia for eight years. She did not use alcohol, nephrotoxic drugs, or herbal substances. There was no history of kidney disease in her family. Serum creatinine on admission was 1.58 mg/dl and e-GFR was 35.2 ml/min/1.73m2. Liver function tests, Hepatitis B, C and HIV serologies, and serum complement levels were normal. Urinalysis, including microscopic examination, did not reveal any abnormality. In 24-hour collected urine 143 mg proteinuria was detected. Kidney biopsy revealed global sclerosis in glomeruli, nucleomegaly, intranuclear inclusions, and hyperchromasia in tubules epithelial cells and endothelial cells. A pathological diagnosis of KIN was made. The genetic analysis detected c.1972 C&gt;T (p. Arg658Trp) mutation in the FAN1 gene. According to the HGMD guideline this variant is classified as an unknown significance. However, the clinical and pathological features of the patient were compatible with KIN, we concluded this specific FAN1 mutation was associated with the disease in our case. Conclusion Despite similar clinical features and histopathological findings, we found two different gene mutations in these two cases. It is especially interesting that UMOD mutation which was associated with hyperuricemia and uric acid nephropathy was associated with KIN. KIN should be included in the differential diagnosis of patients without a definite diagnosis of CKD, the genetic examination should be carried out to reveal the underlying mutation.

Phenotypes of professional bronchial asthma from the standpoint of spirometry

The aim of the study was to conduct a comparative analysis of spirometric indicators of respiration in various phenotypes of occupational bronchial asthma. Materials and methods. At the clinical stage of the work, a comprehensive clinical, radiological, spirographic, echocardiographic, immunological and molecular genetic examination of 170 patients of the main groups and 50 individuals of the control group was carried out. The results of the study. Dynamic determination of the speed indicators of forced exhalation in various phenotypes of occupational bronchial asthma can improve the diagnosis of obstructive disorders in this pathology, optimize the choice of treatment tactics, and predict the course of this pathology.