[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.

[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.

[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.

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.

Identification of large deletions in the APC gene in Russian patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a hereditary syndrome characterized by the presence of multiple adenomatous polyps in the colon. The main cause of the disease is a germline mutation in the APC gene. Here we report 4 unrelated FAP patients with different large deletions in the APC gene detected by Multiplex Ligation-dependent Probe Amplification (MLPA) method: deletion of exons 7-15, deletion of promoters B, A, and 5'-UTR region and deletion of promoter B (in 2 patients). The deletion of promoters B, A, and 5'-UTR was not described in the literature earlier, so we report it for the first time. In 2 families with promoter B deletion, we could identify the tendency for decreasing the age of disease manifestation in each next generation, in contrast to the previous one. The incidence of large deletions in APC among Russian patients with FAP reached 4.8% and our finding suggests the need to study this gene by MLPA in "no mutation patients" after Sanger's sequencing.

Peculiarities of Pharmacokinetics and Bioavailability of Some Cardiovascular Drugs under Conditions of Antiorthostatic Hypokinesia.

We studied pharmacokinetics and bioavailability of verapamil, propranolol, and ethacizine in healthy volunteers after single oral administration under normal conditions and on the second day of simulated antiorthostatic hypokinesia modeling some effects of microgravity. Under conditions of antiorthostatic hypokinesia, a tendency to a decrease in half-elimination period, mean retention time, and volume of distribution and an increase in the rate of absorption, ratio of maximum concentrations, and relative rate of absorption of verapamil and propranolol were revealed. For ethacizine, a statistically significant increase in the time of attaining maximum concentration and volume of distribution and a decrease in the maximum concentration, rate of absorption, ratio of maximum concentrations, and relative rate of absorption under conditions of antiorthostatic hypokinesia were found.

[Cavernous malformation of the optic nerve: clinical case and literature review]. / Kavernoznaia mal'formatsiia zritel'nogo nerva: sluchai iz praktiki i obzor literatury.

INTRODUCTION: Cavernous malformation (cm) of the optic nerve is a rare condition It is clinically presented by the so-called chiasmal apoplexy. Microsurgical removal of cavernous malformation is the method of choice. MATERIAL AND METHODS: Authors present a clinical case of the removal of cavernous malformation of the left optic nerve. RESULTS: The presented case demonstrates the successful removal of the CM of the left optic nerve from the lateral supraorbital access. In the postoperative period, visual disorders did not worsen. Control MRI of the brain showed total removal of cavernoma. CONCLUSION: Presented clinical case demonstrates the radical removal of CM of the optic nerve. Early and correct diagnosis makes it possible to adequately treat the patient and preserve his/her visual functions.

[Hearing loss due to mutations or lack of the gene coding protein stereocillin]. / Narushenie slukha pri mutatsiyakh ili otsutstvii gena, kodiruyushchego belok stereotsilin.

OBJECTIVE: The description of a clinical picture and audiological features at the hearing loss caused by changes of a STRC gene, coding protein stereocillin (MIM: 606440). Mutations in the numerous genes responsible for the inner ear proteins are the reason for congenital sensorineural hearing loss. The main cause of congenital bilateral sensorineural hearing loss in the Russian Federation are mutations in GJB2 gene it reaches up 68% of cases identified in infancy. GJB2 gene tests already became routine around the world. Possibilities of new methods based on sequencing of new generation (NGS, next generation sequencing) allow to conduct a research of more rare genes connected with a hearing impairment. The most often among GJB2 negative patients reveal mutations and deletion of a gene of STRC. PATIENTS AND METHODS: Full audiological examination of 5 children and one adult with a hearing loss from 2 unrelated families is provided. Mutations in STRC gene were identified. All children are examined aged before 8 years, and 3 children failed universal audiological screening in maternity hospital, to two children screening was not carried out as they were born till 2009. RESULTS: The children with the sensorineural hearing loss connected with mutations and deletion of STRC gene failed hearing screening in maternity hospital because of the OAE is not registered, what indicates the congenital nature of a hearing loss. Recently it could not be noticed earlier because of slight increase of hearing thresholds and was regarded only as the early onset. Our data emphasize that the of thresholds from 35 to 60 dB in frequencies 0,5-4 kHz is common for mutations/deletions of STRC gene. CONCLUSION: The development of molecular genetics methods confirms the hereditary causes of GJB2-negative patients and expands indications for family counseling. Special approach for child with hearing loss so early revealed is necessary and the consultation of parents frightened of screening results is very important.

[OTOF-related auditory neuropathy spectrum disorder]. / Zabolevanie spektra auditornykh neiropatii, obuslovlennoe mutatsiyami v gene otoferlina (OTOF).

Otoferlin (OTOF) gene mutations are the most common cause of hereditary ANSD according to investigations in several countries. THE AIM: Of this study was to estimate the prevalence of OTOF mutations in Russian children with ANSD and evaluate audiological and clinical features of OTOF-related ANSD. PATIENTS AND METHODS: 28 children with bilateral ANSDwere enrolled in the investigation. Two step genetic testing was performed: first step - GJB2 gene testing to exclude GJB2-related hearing loss; second step - NGS-based sequencing to explore another 35 hearing loss genes (including OTOF). RESULTS: OTOF mutations, including 6 new variants, were found in 5 children with ANSD (18%). All 5 children had no risk factors for hearing loss and passed hearing screening. OAE and cochlear microphonics were present till the last testing at the age of 4-5 years. ABR were not detectable. The ASSR were measurable bilaterally at all frequencies in all cases, but they did not correlate with behavioral thresholds that revealed severe hearing loss. Hearing thresholds were stable during follow up period. 3 children underwent cochlear implantation. After cochlear implantation auditory nerve action potentials to electric stimulation were detected within normal range. CONCLUSION: Genetic testing of children with ANSD and first of all OTOF testing enables to reveal hearing loss etiology and provide the optimal rehabilitation approach, including cochlear implantation, as early as possible.

Spectrum of CFTR mutations in Chechen cystic fibrosis patients: high frequency of c.1545_1546delTA (p.Tyr515X; 1677delTA) and c.274G>A (p.Glu92Lys, E92K) mutations in North Caucasus.

BACKGROUND: Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mutations can be used to optimize genetic counseling, foster reproductive choices, and facilitate the introduction of mutation-specific therapies. Chechens are a distinct Caucasian ethnic group of the Nakh peoples that originated from the North Caucasus. Chechens are one of the oldest ethnic groups in the Caucasus, the sixth largest ethnic group in the Russian Federation (RF), and constitute the majority population of the Chechen Republic (Chechnya). The spectrum of CFTR mutations in a representative cohort of Chechen CF patients and healthy individuals was analyzed. METHODS: Molecular genetic analysis of 34 CFTR mutations (representing approx. 80-85% of mutations in multiethnic CF populations of the RF) was performed in 32 CF patients from 31 unrelated Chechen families living in Chechnya. One hundred randomly chosen healthy Chechens were analyzed for the 15 most common "Russian" mutations. The clinical symptoms in Chechen CF patients with different CFTR genotypes were investigated. RESULTS: High frequencies of c.1545_1546delTA (p.Tyr515X; 1677delTA) (52 out of 64 CFTR alleles tested; 81.3%) and c.274G > A (p.Glu92Lys, E92K) (8/64, 12.5%) mutations were found. Twenty patients were homozygous for the c.1545_1546delTA mutation, and eight were compound heterozygous for the c.1545_1546delTA and c.274G > A mutations. Three carriers of the c.1545_1546delTA mutation were also found in the cohort of 100 apparently healthy Chechens (frequency - 0.015). The c.1545_1546delTA and c.274G > A mutations are linked to the same haplotype (22-7-16-13) of intragenic Short Tandem Repeat markers, i.e., IVS1CA, IVS6aGATT, IVS8CA, and IVS17bCA. CONCLUSIONS: The distribution of CFTR mutations in the Chechen CF population is unique regarding the high frequency of mutations c.1545_1546delTA and c.274G > A (more than 90% of the mutant alleles). The c.274G > A mutation is associated with a less severe course of CF than that observed in c.1545_1546delTA homozygotes. Testing for these two variants can be proposed as the first step of CF DNA diagnosis in the Chechen population.

[Bilateral supraorbital keyhole approach in surgery of multiple cerebral aneurysms: a case report and literature review]. / Bilateral'nyi supraorbital'nyi keyhole-dostup v khirurgii mnozhestvennykh anevrizm sosudov golovnogo mozga: sluchai iz praktiki i obzor literatury.

The choice of an approach in surgery of bilateral multiple aneurysms is a complex and topical issue. According to the literature data, the occurrence rate of multiple aneurysms varies between 6.5 and 33%. Many authors have proposed various modern microsurgical approaches to reduce the risk of adverse surgical outcomes. The need for surgery in several vascular territories requires a detailed assessment of the topographo-anatomical relationships upon choosing a surgical approach. An important issue is preliminary planning and personalization of an approach for a particular patient. MATERIAL AND METHODS: We report a case of clipping of mirror middle cerebral artery aneurysms using a minimally invasive bilateral approach. RESULTS: The presented case demonstrates successful clipping of middle cerebral artery aneurysms in different vascular territories using the bilateral supraorbital approach: a skin incision along the eyebrow followed by supraorbital keyhole craniotomy. Follow-up CT angiography in the postoperative period demonstrated elimination of aneurysms from the bloodstream. The cosmetic effect after the intervention was evaluated as excellent. CONCLUSION: The bilateral supraorbital approach in surgery of multiple mirror aneurysms may be recommended as an alternative to the contralateral or bilateral pterional approach. The bilateral supraorbital approach avoids additional traction of the frontal lobes, provides a focused personalized approach, and is a safe and effective approach with excellent cosmetic results.

[The transpalpebral keyhole approach in surgery of orbital cavernomas: a case report and literature review]. / Transpal'pebral'nyi keyhole-dostup v khirurgii kavernom orbity: sluchai iz praktiki i obzor literatury.

AIM: Currently, there are many different surgical approaches to orbital pathology. This pathology rarely occurs in neurosurgical practice, and neurosurgeons have often used approaches that can be accompanied by negative cosmetic and functional outcomes. MATERIAL AND METHODS: We present a case report of orbital cavernoma removal via a minimally invasive approach. RESULTS: The presented case demonstrates successful removal of orbital cavernoma using the transpalpebral approach: a skin incision along a natural fold of the upper eyelid and orbitofrontal keyhole craniotomy. In the postoperative period, existing symptoms regressed; the patient assessed the cosmetic effect as excellent. CONCLUSION: The transpalpebral keyhole approach can be an excellent alternative to traditional approaches to orbital cavernomas. This approach demonstrated its efficacy and safety in skull base surgery and provided excellent functional and cosmetic outcomes.

[Endoscope-assisted keyhole approach in cerebral aneurysm surgery]. / Éndoskopicheskaia assistentsiia pri keyhole-dostupakh v khirurgii tserebral'nykh anevrizm.

The last decades in neurosurgery have been marked by the rapid development of minimally invasive techniques, including the use of the concept of keyhole/burrhole surgery and active introduction of endoscopic techniques. These alternatives to traditional approaches have minimized concomitant injury to tissues and the brain and improved functional and cosmetic outcomes. Endoscopic assistance in keyhole approaches, along with its use in traditional approaches, seems even more reasonable because the field of microscopic view is considerably limited in the case of a mini-approach. AIM: We present our experience of using endoscopic assistance (EA) in aneurysm surgery through supraorbital and transorbital keyhole approaches. MATERIAL AND METHODS: We describe the surgical technique, indications for EA, and possible complications. In the period between 2014 and 2107, we used EA in the surgical treatment of 40 patients with cerebral aneurysms of the internal carotid (37 patients) and basilar (3) arteries. In all cases, 0 and 30° rigid endoscopes were used. The EA technique involved standard stages: assessment of anatomy before clipping and assessment after clipping. In 5 (12.5%) patients, clipping was performed under endoscopic visualization. The follow-up period was 6-12 months, on average. RESULTS: All patients underwent successful clipping of aneurysms without neurological complications. There was no death, disability, or serious permanent approach-associated complications in the study group. CONCLUSION: EA is a safe and effective technique providing additional visualization in keyhole surgery of aneurysms.

[Transpalpebral craniotomy in skull base surgery]. / Transpal'pebral'naia kraniotomiia v khirurgii osnovaniia cherepa.

The concept of minimally invasive neurosurgery has significantly evolved in recent years, which is associated with improvements in diagnostics, microneurosurgical techniques, anesthesiology, and intraoperative imaging. MATERIAL AND METHODS: We present the preliminary results of using transpalpebral craniotomy in surgery of supratentorial aneurysms and anterior cranial fossa tumors. In the period between 2015 and 2107, we used this approach in surgical treatment of 30 aneurysms (10 aneurysms in the 'cold' period of hemorrhage and 20 unruptured aneurysms) and 10 anterior cranial fossa base tumors. The approach included a superior eyelid incision and a fronto-orbital craniotomy. We retrospectively evaluated outcomes, postoperative complications, and cosmetic results after these operations. The mean follow-up period was 6 months. RESULTS: There were no deaths, disabilities, or serious permanent approach-associated complications. All patients had expected periorbital edema that was not considered as a complication. CONCLUSION: Transpalpebral craniotomy is a safe and effective approach to anterior cranial fossa neoplasms and anterior circle of Willis aneurysms. This approach avoids injury to the frontal and temporal muscles as well as to the facial and trigeminal nerve branches. Patients assessed the postoperative cosmetic result as excellent.

[Twenty years of clinical studies of GJB2-linked hearing loss in Russia]. / 20 let izucheniia klinicheskikh proiavlenii GJB2-obuslovlennoi tugoukhosti v Rossii.

The most common cause of congenital hereditary hearing loss was discovered 20 years ago in 1997 when GJB2 gene was revealed in the first locus of recessive hearing loss DFNB1. It encodes protein connexin 26, a structural component of the intercellular channels. Recessive mutations in this gene cause the congenital bilateral sensorineural hearing loss. For many years the aim of our work was to study the prevalence and clinical manifestations of hereditary hearing loss. Our research can be divided into three stages. In the beginning, we investigated the prevalence of GJB2 mutations in a healthy population and in the people suffering from hearing impairment. Further research was conducted in the field of clinical manifestations and evidence of the congenital character of GJB2-related hearing loss. Currently, we are working on the prevalence of mild and moderate hereditary hearing loss and the probability of its progression. Achievements in molecular genetics make it possible to establish the hereditary character of congenital hearing loss and to avoid repeated family cases. Primary prevention of hereditary hearing loss becomes real by raising the awareness of GJB2 mutations carriers.

[Epidemiology of hearing loss in children of the first year of life]. / Épidemiologiia narushenii slukha sredi detei 1-go goda zhizni.

The aim of this study was the investigation of the epidemiology of permanent hearing impairment in the children of first year of life in the Russian Federation after the implementation of the newborn universal hearing screening program. The prevalence of hearing loss in children in the first year of life was estimated at 2.5 per 1,000 based on the official statistical data and reports of hearing rehabilitation centres in 2016. A cohort of 405 children born in 2012 was examined at the age from 0 to 4 years of life. Among them 276 children were diagnosed with permanent congenital and prelingual hearing loss. 88% of the cases were bilateral, sensorineural hearing loss confirmed in 84% of the cases. The genetic cause of hearing loss was revealed in 58% of the patients assessed for the presence of GJB2 gene mutations. In preterm infants, the permanent hearing loss was detected in 70% of the cases. The comprehensive audiological assessment before 3 months of life was conducted only in 32% of the children; this finding is not consistent with the international newborn hearing screening recommendations. Only 70% of the cases of congenital and preverbal hearing loss were diagnosed during the first year of life.

[The analysis of the association of the polymorphic variants of the TPMT, COMT, and ABCC3 genes with the development of hearing disorders induced by the cisplatin treatment]. / Analiz assotsiatsii polimorfnykh variantov genov TPMT, COMT i ABCC3 c razvitiem narusheniia slukha, indutsirovannogo priemom tsisplatina.

Cisplatin and its derivatives are widely used chemotherapeutic agents for the treatment of many cancers, including hepatoblastoma, brain tumors, and germ-cell tumors. This therapy contributed to the dramatic increase in the survival rate. However, its use is restricted by the high incidence of irreversible ototoxicity associated with cisplatin application (in more than 60% of the children receiving it). Some studies have reported that genetic variants of TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640) are conferring increased risk of developing cisplatin-induced hearing loss. However, in other studies the results were not replicated. In the present study, we replicated the previous studies based on an independent cohort of Russian patients. SNP genotypes for rs 12201199, rs4646316 and rs 1051640 were determined in DNA samples obtained from 16 patients who developed hearing loss and a group of 34 patients whose hearing was retained. The association between TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640) variants and the hearing loss was not observed in our cohort.

[Results of molecular genetic testing in Russian patients with Pendred syndrome and allelic disorders].

Pendred syndrome is an autosomal recessive inherited disorder characterized by a combination of sensorineural hearing impairment and euthyroid goiter; its clinical manifestation in children is hardly distinguishable from nonsyndromic hearing loss. Pendred syndrome is one of the most frequent types of syndromic hearing loss. Hearing impairment is accompanied by abnormal development of the bony labyrinth­enlarged vestibular aqueduct (EVA) and occasionally combined with Mondini dysplasia. Mutations in the SLC26A4 gene, which encodes the pendrin protein, are responsible for both Pendred syndrome and for allelic disorder (nonsyndromic enlarged vestibular aqueduct). The present study for the first time conducted molecular genetic analysis in 20 Russian patients with Pendred syndrome, EVA and/or Mondini dysplasia. As a result, six pathogenic mutations in the SLC26A4 gene were revealed in four patients. The mutation c.222G>T (p.Trp74Cys) was detected for the first time. Mutations were found in patients with Pendred syndrome and nonsyndromic EVA with or without Mondini dysplasia. Mutations were not detected in patients with isolated Mondini dysplasia. One proband with clinical diagnosis Pendred syndrome was homozygous for the c.35delG mutation in the GJB2 gene. The absence of frequent mutations, including well-known ones or "hot" exons in the SLC26A4 gene, was reported. Therefore, the optimal method to search for mutations in the SLC26A4 gene in Russian patients is Sanger sequencing of all exons and exon-intron boundaries in the SLC26A4 gene.