Orphan diseases (mucopolysaccharidosis) and damage of the cardiovascular system. Literature review

The paper presents literature data, outlining topical issues of the cardiovascular pathology at mucopolysaccharidosis. It is damage to the heart and blood vessels, one of the cardinal signs of this pathology, that is often fatal. Cardiac pathology is recorded in all types of mucopolysaccharidosis, but it is most significant for patients with three clinical variants of Hurler syndrome, Hunter, and Maroteaux–Lamy syndromes. Typical signs of damage to the cardiovascular system in mucopolysaccharidosis are thickening of the valves with the development of their dysfunction (while the severity of damage to the left‑sided valves is more pronounced), myocardial hypertrophy, conduction disturbance, coronary artery disease, arterial hypertension. Many researchers emphasize the difficulties of clinical and functional examination of the cardiovascular system in patients with mucopolysaccharidosis, which is due to the presence of physical and intellectual limitations in patients, and a gradual symptoms aggravation. For the treatment of cardiovascular pathology at mucopolysaccharidosis, medical and surgical methods are used, including enzyme replacement therapy and stem cell transplantation. Gene therapy is considered one of the priority areas in the treatment of mucopolysaccharidosis. Significant progress in this aspect has been achieved with the use of viral vectors under experimental conditions in mice with mucopolysaccharidosis type VII. The basis of mucopolysaccharidosis prevention is medical and genetic counseling of families with subsequent prenatal diagnosis using molecular genetic methods (eg, DNA diagnosis). Thus, early diagnosis and timely pathogenetic treatment of mucopolysaccharidosis will help to prevent disability and adequate integration into society, and effective medical and genetic counseling of families will significantly reduce the incidence of new cases of these severe inherited diseases.

CLINICAL CASES OF BULLOUS EPIDERMOLYSIS IN NEWBORNS

Summary. Hereditary bullous epidermolysis (BE) is a group of genetically and clinically heterogeneous diseases characterized by the formation of blisters and erosion due to injury on the skin and mucous membranes. Different forms of BE can be accompanied by various extracutaneous complications, such as blisters and erosion on the cornea and mucous membranes, stenoses and strictures of the respiratory system, gastrointestinal tract, urinary system, muscular dystrophy, and malignant tumors. Hereditary bullous epidermolysis is divided into three types, depending on the level of blister formation: simple, borderline, and dystrophic. Simple BE is characterized by the stratification of epidermis due to the keratinocyte cytolysis. Borderline BE means that blisters are formed at the border of the epidermis and dermis due to the splitting of the lamina of the basement membrane (lamina lucida), while dystrophic BE has blisters that are formed under the dense plate of the basement membrane (lamina densa), which exfoliates the dermis. Currently, mutations have been identified in more than 10 genes encoding the structural proteins of keratinocytes and the basal membrane of the skin and mucous membranes. A common feature of these proteins is their involvement in the formation of strong bonds between the epithelium and the basement membrane. The nature of the mutations and their localization determine the severity of the clinical manifestations of BE. Mutation information is a prerequisite for effective medical and genetic counseling, prenatal and preimplantation DNA diagnosis. Therefore diagnosis and prescribing appropriate treatment and follow-up care is an important task for neonatologists and pediatric dermatologists. As manifestations of hereditary BE are numerous, a specialized center is required for optimal care, where multidisciplinary care will be provided (neonatologists, pediatric surgeons, pediatric dermatologists, etc.). The purpose of clinical observation is to pay attention of specialists to this rare disease, and to present 2 clinical cases of bullous epidermolysis in newborns who were admitted to the anesthesiology and intensive care unit of newborns of Vinnytsia Regional Children's Clinical Hospital almost at the same time.

A sporadic case of congenital aniridia caused by pericentric inversion inv(11)(p13q14) associated with a 977 kb deletion in the 11p13 region

Background Because of the significant occurrence of “WAGR-region” deletions among de novo mutations detected in congenital aniridia, DNA diagnosis is critical for all sporadic cases of aniridia due to its help in making an early diagnosis of WAGR syndrome. Standard cytogenetic karyotype study is a necessary step of molecular diagnostics in patients with deletions and in the patients’ parents as it reveals complex chromosomal rearrangements and the risk of having another affected child, as well as to provide prenatal and/or preimplantation diagnostics. Case presentation DNA samples were obtained from the proband (a 2-year-old boy) and his two healthy parents. Molecular analysis revealed a 977.065 kb deletion that removed loci of the ELP4, PAX6, and RCN1 genes but did not affect the coding sequence of the WT1 gene. The deletion occurred de novo on the paternal allele. The patient had normal karyotype 46,XY and a de novo pericentric inversion of chromosome 11, inv(11)(p13q14). Conclusions We confirmed the diagnosis of congenital aniridia at the molecular level. For the patient, the risk of developing Wilms’ tumor is similar to that in the general population. The recurrence risk for sibs in the family is low, but considering the possibility of gonadal mosaicism, it is higher than in the general population.

Prenatal diagnosis of spinal amyotrophy

The first regional case of pregnancy management in a patient with a child with spinal muscular atrophy is presented. In the present pregnancy for the purpose of prenatal diagnosis of spinal amyotrophy at 12 weeks transabdominal aspiration of chorion villi was performed, followed by molecular genetic research, which revealed the deletion of exons 7–8 of the SMN 1 gene (survival motor neuron) in the homozygous state. Due to the unfavorable prognosis abortion was performed for medical reasons. Thus, to reduce the risk of having a child with spinal muscular atrophy in families with identified mutations in the SMN 1 gene, prenatal DNA diagnosis of this hereditary pathology is recommended.

Visual DNA diagnosis of Tomato yellow leaf curl virus with integrated recombinase polymerase amplification and a gold-nanoparticle probe

A visual DNA diagnosis with a rapid and simple procedure has been developed on integrating recombinase polymerase amplification (RPA) and a gold nanoparticle (AuNP) probe. The entire process is implemented in only one tube with no precision instrument and requires in total 20 min to amplify a DNA fragment with RPA and to discriminate a DNA fragment with an AuNP probe. The result in various colors is directly observable with the naked eye. Through discovering a small DNA fragment of Tomato yellow leaf curl virus (TYLCV), this system can detect one copy per microlitre of virus in a pure isolate of extracted DNA and can readily identify an infected plant with a healthy appearance. This system hence provides a highly sensitive and stable DNA diagnosis. This visual method has a potential for disease diagnosis and prognostication in the field based on advantages of simplicity, high speed, portability and sensitivity.