TY - JOUR AU - Jimoh, Idris János AU - Balicza, Péter AU - Szlepák, Tamás AU - Csabán, Dóra AU - Gál, Anikó AU - Geresi, Adrienn AU - Grosz, Zoltán AU - Palásti, Ágnes AU - Boczán, Judit AU - Klivényi, Péter AU - Molnár, Mária Judit TI - Expanding the Phenotypic Spectrum of SPG7 Rare Damaging Variants. Insights From a Hungarian Cohort TS - Insights From a Hungarian Cohort JF - CLINICAL GENETICS J2 - CLIN GENET VL - 108 PY - 2025 IS - 2 SP - 124 EP - 133 PG - 10 SN - 0009-9163 DO - 10.1111/cge.14719 UR - https://m2.mtmt.hu/api/publication/35791980 ID - 35791980 N1 - Semmelweis Egyetem, Institute of Genomic Medicine and Rare Disorders, Budapest, Hungary Szegedi Tudományegyetem (SZTE), Doctoral School of Interdisciplinary Medicine, Szeged, Hungary Hungarian Research Network, HUN-REN Multiomics Neurodegeneration Research Group, Budapest, Budapest, Hungary Debreceni Egyetem, Department of Neurology, Debrecen, Hajdu-Bihar, Hungary Szegedi Tudományegyetem (SZTE), Department of Neurology, Szeged, Hungary Szegedi Tudományegyetem (SZTE), Danube Neuroscience Research Laboratory, Szeged, Hungary Export Date: 08 December 2025; Cited By: 1; Correspondence Address: M.J. Molnar; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary; email: molnar.mariajudit@semmelweis.hu; CODEN: CLGNA AB - Mitochondria-associated paraplegin dysfunction is primarily linked to spastic paraplegia; however, genetic alterations in SPG7 have been associated with a broader spectrum of clinical symptoms. To identify disease-causing variants in the SPG7 gene, 437 patients with spastic ataxia, mitochondrial dysfunction-associated symptoms, or motoneuron lesions detected by EMG have been tested. We aimed to assess the clinical spectrum and determine the frequency of damaging variants within patient groups, particularly those less studied. Using ACMG criteria, we identified 10 pathogenic or likely pathogenic variants, 5 variants of uncertain significance with predicted damaging effects, and a probable risk factor variant in 58 patients. We identified 25 biallelic and 33 monoallelic cases. The most common variant was p. Leu78Ter (N = 23), followed by p. Ala510Val (N = 21). The point prevalence of SPG7-associated conditions in Hungary in 2024 is 0.46 per 100 000. In addition to well-characterized cohorts, SPG7 alterations were frequently identified in cohorts with multisystemic mitochondrial disease and lower motoneuron lesions. Multiple mtDNA deletions and histological abnormalities were consistently observed across all groups. In monoallelic cases, no evidence of a digenic effect involving AFG3L2 was found. Both autosomal dominant and recessive inheritance patterns were documented, with monoallelic cases typically presenting with a milder phenotype. LA - English DB - MTMT ER - TY - CONF AU - Jimoh, Idris János AU - Balicza, Péter AU - Gál, Anikó AU - Molnár, Mária Judit TI - MELAS syndrome in Hungary: insights from clinical characteristics and longitudinal follow-up T2 - ESHG European Human Genetics Conference PY - 2025 UR - https://m2.mtmt.hu/api/publication/36313312 ID - 36313312 AB - Background: MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) syndrome is a mitochondrial DNA disease characterized by a systemic disturbance in oxidative phosphorylation. The disease exhibits a wide clinical spectrum and significant phenotypic variability, even within families. The estimated global prevalence of m.3243A>G-associated MELAS varies widely (0.2-236/100,000). Diagnostic and therapeutic challenges are compounded by the broad symptom spectrum and the fluctuating nature of the disease.Material and Methods: We aimed to describe the clinical characteristics of MELAS patients diagnosed with the rare m.3243A>G variant in Hungary. We investigated intrafamilial phenotypic variability, the correlation between heteroplasmy levels and disease onset, and the relationship between symptom progression and patient outcomes. Data were collected from 27 patients (9 males, 18 females) across 17 families. In addition to deep phenotyping and clinical assessment, longitudinal follow-up data from 18 patients were analyzed over a mean period of 5.99 (±4.41) years. Results: The mean age of symptom onset was 33 (±13.21) years, with five childhood cases. Genetic diagnosis was confirmed in 24 cases using blood-derived DNA and in three using muscle-derived DNA. The mean heteroplasmy rate from blood-derived DNA was 32.46% (±14.69%). The average diagnostic time was 7.15 (±6.61) years. Apart from primary myopathic symptoms, initial manifestations primarily included well-established comorbidities such as diabetes and hearing impairment, even in patients with heteroplasmy as low as 15%. Conclusion: Our cohort's phenotypic spectra, combined with clinical data offer valuable insights to refine diagnostic markers, optimize patient pathways, and long-term prognosis. LA - English DB - MTMT ER - TY - JOUR AU - Jimoh, Idris János AU - Palásti, Ágnes AU - Molnár, Viktor AU - Arányi, Zsuzsanna AU - Grosz, Zoltán AU - Molnár, Mária Judit TI - The phenotypic spectra of Hungarian patients with late-onset Tay-Sachs disease: presenting symptoms, patient routes, disease progression and therapeutic experience JF - EUROPEAN JOURNAL OF HUMAN GENETICS J2 - EUR J HUM GENET VL - 32 PY - 2024 IS - Suppl. 2 SN - 1018-4813 UR - https://m2.mtmt.hu/api/publication/36313421 ID - 36313421 AB - Background/Objectives: Tay-Sachs disease is a rare neurogenetic disease caused by pathogenic variants of the HEXA gene. The disease can be divided into juvenile, infantile, and late-onset (LOTS) forms that are associated with different residual enzyme activities. The identification of LOTS patients still remains a diagnostic challenge due to the wide range of presenting symptoms and different patient routes. Thus, despite the long history of the disease, characterization of late-onset patients is still lacking. We aimed to demonstrate the phenotypic spectra of Hungarian LOTS patients. Methods: We demonstrate a case series of 3 patients. Deep-phenotyping by physical examination, MRI, EMG, myopathology, enzyme activity, and detailed follow-up were performed. Results: The presenting symptoms varied. Patient1 with homozygous p.Gly269Ser variant had initially psychotic symptoms from the age of 18, followed by muscle weakness twelve years later, whereas Patient2 with compound heterozygous p.Gly269Ser and p.Ser215Asn variants had presenting symptoms of ataxia, mild paraparesis, and dysthymia since the age of 30 years, Patient3 had compound heterozygous p.Gly269Ser and p.Tyr427Ilefs*5 variants causing muscle hypotrophy and paraparesis since the age of 18 years. One of the patients has been treated with Miglustat for 1.5 years resulting in stabilization of his symptoms. Conclusion: With the patient’s different phenotypes, we can demonstrate, the wide phenotypic spectra in which neurogenic muscle weakness and psychiatry symptoms can be the red flags. The p.Gly269Ser rare variant is common in the Ashkenazi population but it is commonly identifiable in Hungary as well in LOTS. LA - English DB - MTMT ER - TY - JOUR AU - Jimoh, Idris János AU - Molnár, Mária Judit TI - A mitochondrialis betegségek diagnosztikai és kezelési lehetőségei 2021-ben JF - ORVOSTOVÁBBKÉPZŐ SZEMLE J2 - ORVOSTOVÁBBKÉPZŐ SZLE PY - 2022 SN - 1218-2583 UR - https://m2.mtmt.hu/api/publication/32587580 ID - 32587580 LA - Hungarian DB - MTMT ER - TY - JOUR AU - István, Lilla AU - Benyó, Fruzsina AU - Csorba, Anita AU - Jimoh, Idris János AU - Gál, Anikó AU - Molnár, Mária Judit AU - Nagy, Zoltán Zsolt AU - Szabó, Viktória TI - Cornealis polymegathismus és retinalis pigmenthám-eltérések MELAS-szindrómában JF - SZEMÉSZET / OPHTHALMOLOGIA HUNGARICA J2 - SZEMÉSZET VL - 159 PY - 2022 IS - 2 SP - 69 EP - 75 PG - 7 SN - 0039-8101 DO - 10.55342/SZEMHUNGARICA.2022.159.2.69 UR - https://m2.mtmt.hu/api/publication/32990409 ID - 32990409 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Szabó, Fruzsina AU - Grosz, Zoltán AU - Gézsi, András AU - Suveges, Anna AU - Jimoh, Idris János AU - Zeke, Helga AU - Gál, Anikó AU - Molnár, Mária Judit TI - Analysis of the most common nuclear genome encoded mitochondrial gene in Hungarian patients with adult-onset mitochondrial disorders JF - EUROPEAN JOURNAL OF HUMAN GENETICS J2 - EUR J HUM GENET VL - 30 PY - 2022 IS - Suppl.1 SP - 286 EP - 286 PG - 1 SN - 1018-4813 UR - https://m2.mtmt.hu/api/publication/34090032 ID - 34090032 LA - English DB - MTMT ER - TY - JOUR AU - Jimoh, Idris János AU - Balicza, Péter AU - Csabán, Dóra AU - Grosz, Zoltán AU - Varga, N. AU - Molnár, Viktor AU - Fekete, Bálint András AU - Illés, Anett AU - Boczán, Judit AU - Klivényi, Péter AU - Gál, Anikó AU - Molnár, Mária Judit TI - SPG7 mutations in Hungarian cohorts: new insights and possible genotype-phenotype correlations JF - EUROPEAN JOURNAL OF NEUROLOGY J2 - EUR J NEUROL VL - 28 PY - 2021 SP - 845 EP - 845 PG - 1 SN - 1351-5101 UR - https://m2.mtmt.hu/api/publication/32596517 ID - 32596517 AB - Background and aims: Paraplegin encoded by SPG7 causes autosomal recessive hereditary spastic paraplegia (HSP). It is responsible for 5–12% of the HSPs. The SPG7 mutations result in pure HSP, but based on some observations the clinical picture can be more colourful.Methods: We screened 342 Hungarian patients for damaging SPG7 rare variants (DRVs) by NGS. Based on phenotype 5 subcohort were established: spastic paraplegia; ataxia; motoneuron lesion; progressive external ophthalmoplegia, and patient with mitochondrial encephalopathy. We aimed to identify the frequency of the DRVs of the SPG7 in these patients and to compare its ratio in the subgroups.Results: We identified 17 patients with biallelic, 16 patients with monoallelic DRVs. The p.Leu78Ter mutation was present in nine cases with biallelic, in four cases with monoallelic presentation. This DRV seems to be the most common DRV associated with HSP7 in Hungary. In patients with heterozygous presentation is seems to be disease-causing similarly as the p.Ala510Val mutation, which was proposed previously to be associated with HSP in heterozygous form as well. This latter was also common in the Hungarian cohort. The ratio of DRVs was the following in the subgroups: spasticity 11,39%, ataxia 17,61%, motoneuron lesion 7,87%, PEO 11,90%., and mitochondrial encephalopathy 9,64%.Conclusion: SPG7 mutation result in wide clinical phenotype. The p.Leu78Ter DRV is the most common pathogenic mutation in Hungary beside the p.Ala510Val. Both of these DRVs may result in clinical signs both in monoallelic and biallelic form, the monoallelic alterations result in less severe phenotype.Disclosure: The authors have nothing to declare. LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Mária Judit AU - Jimoh, Idris János AU - Zeke, Helga AU - Palásti, Ágnes AU - Fedor, Mariann TI - Early-Onset Schizophrenia With Predominantly Negative Symptoms: A Case Study of a Drug-Naive Female Patient Treated With Cariprazine JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 11 PY - 2020 SN - 1663-9812 DO - 10.3389/fphar.2020.00477 UR - https://m2.mtmt.hu/api/publication/31293409 ID - 31293409 AB - Schizophrenia is a chronic and severe mental disorder characterized by positive, negative, and cognitive symptoms. Negative symptoms are usually present from the prodromal phase; early diagnosis and management of negative symptoms is a major health concern since an insidious onset dominated by negative symptoms is associated with a worse outcome. Antipsychotic medications, which are effective for treating positive symptoms, are generally ineffective for treating negative or cognitive symptoms. We present a 23-year-old woman showing severe symptoms at her first visit to our department. The patient’s parents reported that their daughter had experienced several years of psychosocial decline and putative psychiatric symptoms, but no medical attention had been previously sought; as such, the diagnosis of schizophrenia with predominantly negative symptoms was very much delayed. Early onset of schizophrenia, longer duration of untreated psychosis, and severe negative symptoms, which have limited treatment options, suggested a poor prognosis. We initiated monotherapy with cariprazine, a novel antipsychotic that has recently been proven efficacious in treating schizophrenia with predominantly negative symptoms. This report describes a 52-week cariprazine treatment regimen and follows the patient’s impressive clinical improvement confirmed by PANSS and CGI scores, and psychological tests. LA - English DB - MTMT ER - TY - JOUR AU - Jimoh, Idris János AU - Sebe, Barbara AU - Balicza, Péter AU - Fedor, Mariann AU - Pataky, Ilona AU - Rudas, Gábor AU - Gál, Anikó AU - Inczédy-Farkas, Gabriella AU - Németh, György AU - Molnár, Mária Judit TI - Wernicke–Korsakoff syndrome associated with mtDNA disease JF - THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS J2 - THER ADV NEUROL DISO VL - 13 PY - 2020 IS - January-December PG - 7 SN - 1756-2856 DO - 10.1177/1756286420938972 UR - https://m2.mtmt.hu/api/publication/31409996 ID - 31409996 N1 - Semmelweis University of Medicine, Budapest, Hungary Gedeon Richter Nyrt, Budapest, Hungary Peter Pazmany Catholic University, Budapest, Hungary Northwell Health, NY, United States Semmelweis University of Medicine, Üllői 26, Budapest, 1085, Hungary Cited By :3 Export Date: 26 July 2023 Correspondence Address: Molnar, M.J.; Semmelweis University of Medicine, Üllői 26, Hungary; email: molnarmj@gmail.com LA - English DB - MTMT ER - TY - JOUR AU - Fekete, Bálint András AU - Pentelényi, Klára AU - Rudas, Gábor AU - Gál, Anikó AU - Grosz, Zoltán AU - Illés, Anett AU - Jimoh, Idris János AU - Csukly, Gábor AU - Domonkos, Andor AU - Molnár, Mária Judit TI - Broadening the phenotype of the TWNK gene associated Perrault syndrome JF - BMC MEDICAL GENETICS J2 - BMC MED GENET VL - 20 PY - 2019 IS - 1 PG - 8 SN - 1471-2350 DO - 10.1186/s12881-019-0934-4 UR - https://m2.mtmt.hu/api/publication/31032708 ID - 31032708 AB - Perrault syndrome is a genetically heterogenous, very rare disease, characterized clinically by sensorineural hearing loss, ovarian dysfunction and neurological symptoms. We present the case of a 33 years old female patient with TWNK-associated Perrault syndrome. The TWNK gene is coding the mitochondrial protein Twinkle and currently there are only two reports characterizing the phenotype of TWNK-associated Perrault syndrome. None of these publications reported about special brain MRI alterations and neuropathological changes in the muscle and peripheral nerves.Our patients with TWNK-dependent Perrault syndrome had severe bilateral hypoacusis, severe ataxia, polyneuropathy, lower limb spastic paraparesis with pyramidal signs, and gonadal dysgenesis. Psychiatric symptoms such as depression and paranoia were present as well. Brain MRI observed progressive cerebellar hyperintensive signs associated with cerebellar, medulla oblongata and cervical spinal cord atrophy. Light microscopy of the muscle biopsy detected severe neurogenic lesions. COX staining was centrally reduced in many muscle fibers. Both muscle and sural nerve electron microscopy detected slightly enlarged mitochondria with abnormal cristae surrounded by lipid vacuoles. In the sural nerve, dystrophic axons had focally uncompacted myelin lamellae present. Genetic investigation revealed multiple mtDNA deletion and compound heterozygous mutations of the TWNK gene (c.1196 A > G, c.1358 G > A).This study demonstrates that TWNK associated Perrault syndrome has a much broader phenotype as originally published. The coexistence of severe hypoacusis, spastic limb weakness, ataxia, polyneuropathy, gonadal dysgensia, hyperintense signals in the cerebellum and the presence of the mtDNA multiple deletion could indicate the impairment of the TWNK gene. This is the first report about pyramidal tract involvement and cerebellar MRI alteration associated with TWNK-related Perrault syndrome. LA - English DB - MTMT ER -