Genetic Features of Tongue Cancer Recurrence in Young Adults.

To identify genetic alterations associated with tongue cancer recurrence in young adults, whole exome sequencing of the primary tumor, recurrence, and whole blood samples from young patients with tongue cancer was performed. A frameshift mutation in the TP53 gene was detected in the primary tumor and recurrence tumor tissue. A mutation in the EPHB6 gene was detected in the recurrence and was absent in the primary tumor. In addition, the primary tumor and recurrence tongue cancer tissue harbored amplification of the 20p13 region containing C20orf96, DEFB125, DEFB126, DEFB127, DEFB128, DEFB129, DEFB132, and ZCCHC3 genes. Thus, genetic alterations have been identified that are associated with tongue cancer recurrence in young adults.

[Repeated liver resections for recurrent intrahepatic cholangiocarcinoma]. / Povtornye rezektsii pecheni pri retsidive vnutripechenochnoi kholangiokartsinomy.

OBJECTIVE: To evaluate the safety and advisability of repeated liver resection (RLR) for recurrent intrahepatic cholangiocarcinoma (ICC). MATERIAL AND METHODS: The results of RLR for ICC recurrence (n=10) were retrospectively analyzed between 1999 and 2023. The control group consisted of patients undergoing primary liver resection for ICC (n=195). RESULTS: Surgery time (p=0.001) and blood loss (p=0.038) were lower in the RLR group. There were no blood transfusions (0 vs. 31.8%, p=0.034) and 90-day mortality (0 vs. 3.2%, p=1.0) in the same group. The risk of complications (30.0% vs.45.6%, p=0.517) and adverse events grade ≥ III (20.0% vs. 17.9%, p=1.0) was similar in both groups. Multifocal intrahepatic nodes were more common in the RLR group (60% vs. 37.9%, p=0.193), while there were no negative factors such as lymph nodes involvement (0 vs. 34.4%, p=0.032) and invasion of surrounding structures (0 vs. 38.5%, p=0.015). Dimensions of the largest node were smaller in repeated resection (2 vs. 8 cm, p<0.0001). Incidence of R0 resections (80.0% vs. 82.1%, p=1.0) was comparable. Long-term results were similar: five-year overall survival 17.2% and 34.7% (p=0.912), three-year disease-free survival 20.0% and 26.5% (p=0.421). CONCLUSION: Similar results of repeated and primary liver resections confirm advisability of RLR for intrahepatic recurrence of ICC.

[Surgical treatment and prognostic factors in perihilar tumors]. / Khirurgicheskoe lechenie i faktory prognoza pri perikhilyarnoi opukholi.

OBJECTIVE: To study the results of surgical treatment in patients with perihilar tumors. MATERIAL AND METHODS: We analyzed 98 patients with perihilar tumors who underwent surgery. RESULTS: We prefer percutaneous transhepatic biliary drainage (n=58) for jaundice. Retrograde interventions were performed in 18 cases (20.5%), complications grade III-IV were more common (p=0.037) in the last group. Postoperative mortality was 12%. Complications developed in 81 patients (82.7%), grade ≥3 - in 39 (39.8%) cases. Portal vein resection (n=26) increased the incidence of complications grade ≥III (p=0.035) and portal vein thrombosis (p=0.0001). Chemotherapy after surgery was performed in 47 patients (48.0%), photodynamic therapy - in 7 (7.1%) patients. A 5-year overall survival was 28.1%, the median survival - 29 months. R2 resection and/or M1 stage (n=12) significantly worsened the prognosis and overall survival (16.5 vs. 31 months, p=0.0055). Lymph node (LN) lesion, microscopic status (R0 vs. R1) of resection margin, technique of decompression and isolated resection of extrahepatic bile ducts did not affect the prognosis, and we combined appropriate patients (n=72) for analysis. SI resection and excision of ≥6 lymph nodes were independent positive factors for disease-free survival (p=0.042 and p=0.007, respectively). Blood transfusion and high preoperative neutrophil-lymphocyte index (NLI ≥2.15) worsened overall (p=0.009 and p=0.002, respectively) and disease-free survival (p=0.002 and 0.007, respectively). The absence of adjuvant therapy worsened disease-free survival alone (p=0.024). CONCLUSION: SI liver resection, adequate lymph node dissection and adjuvant therapy should be used for perihilar tumors. Isolated resection of extrahepatic bile ducts is permissible in some cases. Blood transfusion and NLI ≥2.15 are independent negative prognostic factors.

[Anterior transpetrosal (Kawase) approach for petroclival meningioma with trigeminal neuralgia: case report and literature review]. / Perednii transpiramidnyi dostup (dostup Kawase) pri petroklival'noi meningiome s trigeminal'noi nevralgiei: opisanie klinicheskogo nablyudeniya i obzor literatury.

The authors present a patient with petroclival meningioma complicated by trigeminal neuralgia. Resection of tumor via anterior transpetrosal approach with microvascular decompression of the trigeminal nerve was performed. A 48-year-old female patient presented with left-sided (V1-V2) trigeminal neuralgia. Magnetic resonance imaging revealed a tumor 33´27´25 mm with a base adjacent to the top of petrous part of the left temporal bone, tentorium cerebelli and clivus. Intraoperative examination revealed true petroclival meningioma extending to trigeminal notch of petrous part of temporal bone. There was additional compression of trigeminal nerve by caudal branch of superior cerebellar artery. Total resection of tumor was followed by disappearance of vascular compression of trigeminal nerve and regression of trigeminal neuralgia. Anterior transpetrosal approach provides early devascularization and resection of true petroclival meningioma, as well as wide imaging of anterolateral surface of the brainstem, identification of neurovascular conflict and vascular decompression.

[Laparoscopic distal pancreatectomy for portal annular pancreas]. / Laparoskopicheskaya distal'naya rezektsiya podzheludochnoi zhelezy pri portal'noi kol'tsevidnoi podzheludochnoi zheleze.

Portal annular pancreas is a little-known anatomical variant of annular pancreas. In these patients, pancreatic parenchyma encircles the portal vein annularly. This anomaly is associated with high risk of postoperative pancreatic fistula in pancreatic surgery. Considering small incidence of anomaly and characteristics of surgery, we describe laparoscopic distal pancreatectomy with preservation of spleen and splenic vessels in a patient with solid pseudopapillary tumor combined with portal annular pancreas. A 33-year-old woman underwent laparoscopic surgery for cystic-solid pancreatic tumor. Spleen-sparing distal pancreatectomy was performed. Portal annular pancreas was visualized intraoperatively and confirmed retrospectively after analysis of MR data. Ventral and dorsal parts of portal annular pancreas were transected using stapler device. Pancreatic fistula developed in postoperative period. The patient was discharged after 6 days with a drainage tube. Surgeons need to be aware of portal annular pancreas. This anomaly increases the risk of postoperative fistula. Transection of ventral and dorsal parts of annular pancreas using stapler device is the most acceptable option to reduce the risk of postoperative fistula.

[Irreversible electroporation in locally advanced pancreatic cancer]. / Neobratimaya elektroporatsiya pri mestno-rasprostranennoi adenokartsinome podzheludochnoi zhelezy.

OBJECTIVE: To determine the feasibility of irreversible electroporation (IRE) for locally advanced pancreatic adenocarcinoma. MATERIAL AND METHODS: Twenty-three patients underwent IRE after chemotherapy for locally advanced pancreatic cancer between 2015 and 2022. IRE was performed during laparotomy as a rule (n=22). In one case, IRE was combined with palliative pancretoduodenectomy. Nineteen (86.3%) patients received adjuvant chemotherapy after the procedure. The follow-up examination included contrast-enhanced CT/MRI of the abdomen, chest X-ray or CT, analysis of CA 19-9 marker one month after surgery and then every three months. RESULTS: Complications after IRE developed in 5 (21.7%) patients. Three patients (13.0%) had arrhythmia, two (8.7%) ones had pancreatic necrosis. A 90-day mortality after the procedure was 4.3% (n=1), the cause was pancreatic necrosis. According to intraoperative data and the first examination (CT/MRI), the entire tumor infiltrate was treated in 21 (91.3%) cases. Median follow-up was 19 months. Median period until local recurrence was 15 months. Isolated local recurrence was observed in 7 patients. Of these, 3 ones underwent radiotherapy, one patient underwent repeated IRE. Distant metastases were found in 11 patients; systemic therapy was restarted. Median time to progression was 7 months after IRE and 14 months after initiation of chemotherapy. The median overall survival was 16 months after electroporation and 25 months after chemotherapy. CONCLUSION: Irreversible electroporation may be useful in carefully selected patients with unresectable locally advanced pancreatic adenocarcinoma after successful induction chemotherapy. This procedure provides local control, but the impact on long-term outcomes and feasibility of routine use should be analyzed in randomized trials.

[On the prospects of the impedance monitoring method for determining the prescription of death coming]. / O perspektivnosti metoda impedansometrii dlya opredeleniya davnosti nastupleniya smerti.

The aim of the scientific work is to analyze the prospects of using the impedance monitoring method to determine the prescription of death coming. The conducted exploratory analysis allows hypothesizing the dependence of impedance values and dispersion factors for the diagnostic zones studies on the postmortem interval; it also suggests that it is possible to determine this interval for the objects (pig corpses) studies with a combination of impedance values and the corresponding factors. Among large mammals, a swine is the closest to a human from the point of analyzing the postmortem period process, and it can be recommended as an adequate human corpse model. When determining the correlation between the postmortem interval and the impedance parameters, it is the simplicity and reproducibility of the method, the absence of expensive equipment, its portability and the rapid receipt of results that allow this method to be applied at the scene, reinforcing traditional forensic methods for determining the prescription of death coming. Interpretation of impedance monitoring results can be used to analyze the biological nature of the postmortem period processes.

[On the study of postmortem tissue changes' dynamics according to impedance metrics data]. / K voprosu izucheniya dinamiki postmortal'nykh izmenenii tkanei po dannym impedansometrii.

OBJECTIVE: To find a way and form of presenting impedance metrics data to clarify prescription of death coming in a comprehensive assessment. MATERIAL AND METHODS: The impedance of biological objects was measured depending on prescription of death coming in standardized conditions (air temperature +4 °C, humidity 45%). The main examined postmortem period was 1 months. Measurements were made on 3 diagnostic zones of biological object and for 5 current frequency of the study. A total of 2100 readings were taken. RESULTS AND CONCLUSION: The studies performed in standardized conditions have showed that using impedance metrics method to diagnose prescription of death coming is possible. The analysis of only absolute impedance values is not sufficient to clarify prescription of death coming due to its undulating changes. The additional use of relative coefficients, characterizing impedance dispersion, is suggested. The study of possible using the impedance indicators of corpse's tissues to determine prescription of death coming should be performed with consideration to pathomorphology of degradation. Further study of impedance dynamics when corpse is under different conditions is necessary for development of a working algorithm to determine prescription of death coming based on tissue impedance.

[On using the corpses of large mammals as model objects for studying the postmortem period]. / Ob ispol'zovanii trupov krupnykh mlekopitayushchikh v kachestve model'nykh ob"ektov pri izuchenii postmortal'nogo perioda.

THE AIM OF THE STUDY: Is to justify using the corpses of large mammals as model objects for studying the postmortem period. Similarities in processes occurring postmortem in human and swine corpses (decomposition stages and the structure of dominant necrophilic organisms inhabiting the corpse), as well as similar changes of relative impedance parameters for the cartilaginous tissue and musculoskeletal flap of swine and human corpses have been established. The results obtained allow recommending the swine corpse as an adequate human corpse model both for scientific studies and for solving specific scientific and practical issues arising in the practice of forensic examination when determining the prescription of death coming and the postmortem period conditions.

Differential Markers of Subpopulations of Epithelial Cells of the Larynx in Squamous Cell Carcinoma.

In squamous cell carcinoma of the larynx, the population of epithelial cells in the tumor tissue is initially heterogeneous and, in addition to tumor cells invading the organ mucosa, includes normal epithelial cells of protein-mucous glands and cells of the stratified epithelium covering the mucous membrane. A search for differential markers to separate these subpopulations was carried out. The surface marker CD44 and cytokeratins 5 and 17 that are often used to verify carcinoma cells, are common markers for all epithelial cells of the larynx. In highly differentiated carcinoma, subpopulations of normal and tumor epithelial cells can be separated by the level of expression of cytokeratins 10 and 18 and nuclear markers Ki-67 and p63. However, in moderately differentiated carcinoma, tumor cells and normal cells of the basal layer of the stratified epithelium covering the mucous membrane of the larynx have similar phenotypes, which should be taken into account when conducting experimental studies.

[Successful microsurgical resection of a large brainstem abscess: case report and literature review]. / Uspeshnoe mikrokhirurgicheskoe udalenie abstsessa stvola golovnogo mozga: sluchai iz praktiki i obzor literatury.

OBJECTIVE: To present a patient with brainstem abscess treated by microsurgical resection. CASE PRESENTATION: A 53-years-old female patient admitted to the neurosurgical department in a severe condition with symptoms of intracranial hypertension, hyperthermia, general infectious signs and laboratory manifestations of infectious process. Contrast-enhanced MRI revealed a large brainstem lesion (abscess). Retrosigmoid craniotomy with total microsurgical resection of the abscess was performed. External ventricular drainage was incerted on the second postoperative day due to progressive hydrocephalus with clinical deterioration, it was removed in 8 days. Slow positive dynamics was observed in postoperative period. The patient was discharged in 2 weeks after surgery. CONCLUSION: There are no established algorithm for the treatment of brainstem abscesses. Therapeutic approach is advisable for small abscesses. There are 2 neurosurgical options for this lesion: stereotactic drainage and microsurgical resection with or without external ventricular drainage. Treatment strategy depends on location and size of abscess, as well as clinical state of the patient.

[Gyrate atrophy of the choroid and retina with ornithinemia and foveoschisis (clinical observation)]. / Atrofiya girate khorioidei i setchatki s ornitinemiei i foveoshizisom (klinicheskoe nablyudenie).

Gyrate chorioretinal atrophy (GCA) is a rare hereditary disease with certain complications; one extremely rare complication of GCA is foveoschisis. For the first time in Russian ophthalmology, a 10-year-old female child has been described to have genetically verified GCA associated with the OAT gene in combination with ornithinemia and foveoschisis. The diagnosis was made on the basis of fundus examination, perimetry data, autofluorescence, optical coherence tomography, fluorescence angiography, electroretinography, mass spectrometry with confirmation by molecular genetic research. The presented clinical case illustrates the need for an interdisciplinary approach to the diagnosis of GCA with diagnostic algorithm involving various examination methods and doctors of different specialties.

[Suicide by electric shock with the use of engineering skills]. / Samoubiistvo elektricheskim tokom s primeneniem inzhenernykh navykov.

A case of suicide using technical electricity is presented. The fact of electrical injury is confirmed by the typical macroscopic and microscopic picture of an electric mark. The location of the conductors on the body indicated the victim's knowledge of the effect of electric current on the human body, the ways of its propagation through the body through the vital organs, preparation and determination in the implementation of suicidal intentions. The interest of this case lies in the fact that electrical injury as a method of suicide is extremely rare in expert practice.

How common is add-on use and how do patients decide whether to use them? A national survey of IVF patients.

STUDY QUESTION: What is the prevalence and pattern of IVF add-on use in Australia? SUMMARY ANSWER: Among women having IVF in the last 3 years, 82% had used one or more IVF add-on, most commonly acupuncture, preimplantation genetic testing for aneuploidy and Chinese herbal medicine. WHAT IS KNOWN ALREADY: IVF add-ons are procedures, techniques or medicines which may be considered nonessential to IVF, but usually used in attempts to improve the probability of conception and live birth. The use of IVF add-ons is believed to be widespread; however, there is little information about the prevalence and patterns of use in different settings. STUDY DESIGN, SIZE, DURATION: An online survey was distributed via social media to women in Australia who had undergone IVF since 2017. Women were excluded if they were gestational surrogates, used a surrogate, or underwent ovarian stimulation for oocyte donation or elective oocyte cryopreservation only. The survey was open from 21 June to 14 July 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Survey questions included demographics, IVF and medical history, and use of IVF add-ons including details of the type of add-on, costs and information sources used. Participants were also asked about the relative importance of evidence regarding safety and effectiveness, factors considered in decision-making and decision regret. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1590 eligible responses were analysed. Overall, 82% of women had used one or more add-ons and these usually incurred an additional cost (72%). Around half (54%) had learned about add-ons from their fertility specialist, and most reported that the decision to use add-ons was equally shared with the specialist. Women placed a high level of importance on scientific evidence for safety and efficacy, and half (49%) assumed that add-ons were known to be safe. Most women experienced some regret at the decision to use IVF add-ons (66%), and this was more severe among women whose IVF was unsuccessful (83%) and who believed that the specialist had a larger contribution to the decision to use add-ons (75%). LIMITATIONS, REASONS FOR CAUTION: This retrospective survey relied on patient recall. Some aspects were particularly prone to bias such as contributions to decision-making. This approach to capturing IVF add-on use may yield different results to data collected directly from IVF clinics or from fertility specialists. WIDER IMPLICATIONS OF THE FINDINGS: There is a very high prevalence of IVF add-on use in Australia which may be generalisable to other settings with similar models of IVF provision. Although women placed high importance on scientific evidence to support add-ons, most add-ons do not have robust evidence of safety and effectiveness. This suggests that IVF patients are not adequately informed about the risks and benefits of IVF add-ons, or are not aware of the paucity of evidence to support their use. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a McKenzie Postdoctoral Fellowship Grant (University of Melbourne), a Department of Obstetrics and Gynaecology Innovation Grant (University of Melbourne) and an NHMRC Investigator Grant (APP1195189). A.P. declares that he provides fertility services at Melbourne IVF (part of Virtus Health). J.W. reports grants from Wellcome Trust, during the conduct of the study, and that publishing benefits his career. The remaining authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

[Resection of liver segments VII-VIII: is right hepatic vein reconstruction advisable?] / Rezektsiya VII­VIII segmentov pecheni: est' li tselesoobraznost' rekonstruktsii pravoi pechenochnoi veny?

OBJECTIVE: To improve the treatment outcomes in patients with primary and metastatic liver tumors localized in segments VII-VIII involving the right hepatic vein and its branches. MATERIAL AND METHODS: There were 16 surgical interventions including resection of liver segment VII and/or VIII with resection of the right hepatic vein and its branches without reconstruction. All procedures were carried out at the Department of Liver and Pancreatic Tumors of the Blokhin National Medical Cancer Research Center for the period 2016-2020. The cause of surgery was colorectal cancer liver metastases in 8 patients, hepatocellular carcinoma in 2 cases, angiomyolipoma in 1 case and metastases of uterine cancer in 1 patient. Minor liver resection was additionally performed in 5 cases. RESULTS: Median surgery time was 150 (80-220) min, intraoperative blood loss - 400 (100-2000) ml. Afferent blood flow was blocked in 4 patients for 14 (12-25) min. None patient had intraoperative signs of impaired venous outflow. Biliary fistula in postoperative period occurred in 1 patient. No complications were noted in other cases. Median postoperative hospital-stay was 13 (9-19) days. There were no specific complications in long-term postoperative period that could be associated with venous outflow blockade through the right hepatic vein. CONCLUSION: Existing vessels and intrahepatic collaterals de novo can provide adequate venous outflow into the middle hepatic vein and short hepatic veins during resection of liver segments VII and/or VIII with resection of the right hepatic vein and its branches without reconstruction and the absence of inferior right hepatic vein.

[Efficiency and safety of minimally invasive approaches for microsurgical treatment of brain aneurysms]. / Effektivnost' i bezopasnost' ispol'zovaniya minimal'no invazivnykh dostupov v mikrokhirurgicheskom lechenii tserebral'nykh anevrizm.

Background. Brain aneurysms are found in 1-2% of population and cause subarachnoid hemorrhage (SAH) in 80-85% of cases. In recent decades, the incidence of unruptured aneurysms has increased due to widespread availability of CT and MRI. Microsurgery is still essential in the treatment of cerebral aneurysms. OBJECTIVE: To assess the effectiveness and safety of minimally invasive approaches in microsurgical treatment of brain aneurysms in comparison with traditional approaches, to clarify the indications and contraindications for minimally invasive approaches. MATERIAL AND METHODS: There were 394 patients with cerebral aneurysms for the period 2014-2019. All patients were divided into 2 groups depending on surgical approach: traditional approach (TrA) (n=171, 43.4%) and minimally invasive approach (MiniAp) (n=223, 56.6%). In the TrA group, pterional (n=85), orbitozygomatic (n=23) and lateral supraorbital approaches (n=63) were used. In the MiniAp group, transbrow supraorbital (n=88), mini-pterional (n=62), transbrow transorbital (n=37) and transpalpebral transorbital approaches (n=36) were used. Treatment outcomes were compared in both groups for patients with ruptured and unruptured aneurysms. We evaluated intra- and postoperative complications, surgery time and postoperative hospital-stay. Neurological outcomes were assessed using the Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRs). Cosmetic outcomes were compared using the visual analogue cosmetic scale. Unilateral hypesthesia and eyebrow movement were assessed separately after 3, 6 and 12 months. RESULTS: In acute period of SAH, surgery time was significantly less in the MiniAp group (p=0.001). There were no significant between-group differences in the incidence of intraoperative rupture, surgical and neurological complications (p>0.05). Postoperative hospital-stay was significantly less in the MiniAp group (p=0.006). In this group, neurological outcomes were slightly better (p<0.001), there was no mortality, adverse outcomes occurred in 5.3% of cases (n=5). In the TrA group, 1 patient died from postoperative hematoma, adverse outcomes were noted in 9 (8.7%) patients. Cosmetic outcomes were significantly better in the MiniAp group (p<0.001). In delayed period of SAH and unruptured aneurysms, surgery time was less in the MiniAp group (p=0.051). Incidence of intra- and postoperative complications was similar in both groups (p>0.05). Hospital-stay was significantly shorter in the MiniAp group (p<0.001). Functional outcomes were comparable in both groups. Cosmetic outcomes were significantly better in the MiniAp group (p<0.05). CONCLUSION: MiniAp and TrA are characterized by similar efficacy in microsurgical treatment of cerebral aneurysms. MiniAp is recommended only for experienced neurosurgeons in a specialized hospital. Safety and effectiveness of MiniAp are achieved by careful selection of patients, individual neuroimaging and preoperative planning.

[Unusual case of suicide by hanging from the cab door of a MAN truck]. / Neobychnyi sluchai samoubiistva putem povesheniya na dveri kabiny gruzovogo avtomobilya «MAN¼.

An unusual case of suicide by hanging on the door inside the cab of a truck (truck) «MAN¼ is presented: the neck is squeezed between the edge of the movable glass and the edge of the frame of the car door from the driver's seat. The above observation supplements the existing variants about the possibility of hanging with a kind of one-sided open «loop¼.

[On the possibility of luminol solution usage to detect the blood traces when examining the scene]. / O vozmozhnosti ispol'zovaniya rastvora lyuminola dlya obnaruzheniya sledov krovi pri osmotre mesta proisshestviya.

Objective - to present a comparative analysis of the specialized literature on the possibility of using a luminol solution to detect blood traces when examining the scene of an incident. The use of this sample at the incident scene is only preliminary, since its high sensitivity connected with nonspecific properties. Information about the possibility of identifying the species, group and DNA belonging of blood traces after their treatment with a luminol solution is contradictory, therefore, its use at the scene should be careful with the preservation of intact (not treated with luminol) blood traces available for their study by traditional forensic biological methods. The possibility of laboratory determination of the properties of blood after processing its traces with a luminol solution can be proved by a special scientific and experimental forensic biological work.

KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families.

BACKGROUND: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population. METHODS: Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel 'spastic paraplegias' with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing. RESULTS: AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous KIF1A mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within KIF1A motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. All 4 complicated cases were caused by novel mutations without familial history. The phenotypes varied from severe in two patients (e.g. lack of walking, pronounced mental retardation) to relatively mild non-disabling symptoms in two others. CONCLUSION: AD SPG30 is one of the most common forms of SPG in Russia, the disorder has pronounced clinical variability while pure familial cases represent a significant part.

HINT1 gene pathogenic variants: the most common cause of recessive hereditary motor and sensory neuropathies in Russian patients.

Pathogenic variants in the HINT1 gene lead to hereditary axonopathy with neuromyotonia. However, many studies show that neuromyotonia may remain undiagnosed, while axonopathy is the major clinical finding. The most common cause of neuromyotonia and axonopathy, especially in patients of Slavic origin, is a c.110G>C (p.Arg37Pro) pathogenic variant in homozygous or compound heterozygous state. In this study, we analyzed a peripheral neuropathy caused by pathogenic variants in the HINT1 gene and evaluated its contribution to the hereditary neuropathy structure. The studied group included 1596 non-related families diagnosed with hereditary motor and sensory neuropathy (HMSN). The results show that HINT1 gene pathogenic variants make a significant contribution to the hereditary neuropathy epidemiology in Russian patients. They account for at least 1.9% of all HMSN cases and 9% of axonopathy cases. The most common HINT1 pathogenic variant in Russian patients is the c.110G>C (p.Arg37Pro) substitution. Its allelic frequency is 0.2% (95% CI 0.19-0.21%), carrier frequency is 1 in 250 people in Russian Federation, and the estimated disease incidence is 1 in 234,000 individuals. It was determined that the cause of this pathogenic variant's prevalence is the founder effect.