Neurogenetics最新文献

A recurrent c.953A>C (p. Gln318Pro) variant in ALG11 causing congenital disorder of glycosylation in Turkish population. 一种在土耳其人群中引起先天性糖基化障碍的ALG11中复发的C . 953a >c （p. Gln318Pro）变异。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-05-27 DOI: 10.1007/s10048-025-00826-7

Pinar Ozkan Kart, Oguzhan Demir, Ayberk Turkyilmaz, Alper Han Cebi, Ali Cansu

{"title":"A recurrent c.953A>C (p. Gln318Pro) variant in ALG11 causing congenital disorder of glycosylation in Turkish population.","authors":"Pinar Ozkan Kart, Oguzhan Demir, Ayberk Turkyilmaz, Alper Han Cebi, Ali Cansu","doi":"10.1007/s10048-025-00826-7","DOIUrl":"https://doi.org/10.1007/s10048-025-00826-7","url":null,"abstract":"Congenital disorders of glycosylation type 1p, one of the N-glycosylation defects, Asparagine-dependent glycosylation 11 (ALG11-CDG, #OMIM: 613,666), is a very rare type of autosomal recessive glycosylation defect that causes multisystem involvement and frequently presents with neurological symptoms such as epilepsy and neuromotor developmental delay. In this study, we aimed to present three Turkish patients from three unrelated families with the recurrent variant in the ALG11 gene, along with their clinical and genotypic findings, and to compare them with other cases described in the literature. Three patients from three unrelated families were identified who were comprehensively evaluated with clinical examination, laboratory tests, and imaging studies. The whole exome sequencing (WES) with copy number analysis was performed. The identified variants were confirmed in the proband and parents using Sanger sequencing. Common clinical features of the patients included refractory epileptic seizures, developmental delay, and microcephaly, consistent with the literature. Developmental and Epileptic Encephalopathy starting in the first year of life and burst suppression pattern observed in electroencephalogram are among the important clinical features. WES analysis revealed a homozygous NM_001004127.3: c.953A > C (p. Gln318Pro) missense variant in the ALG11 gene in all three patients. This study presents the clinical and genetic features of three Turkish patients with the ALG11-CDG subtype, which has been previously described in the literature; it reinforces the current knowledge on phenotypic diversity by comparisons with similar cases. In addition, the role of WES in the diagnosis of rare CDG subtypes has been demonstrated once again.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"46"},"PeriodicalIF":1.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A heterozygous variation of PINK1 is potentially associated with essential tremor in a Chinese family. PINK1的杂合变异可能与中国一个家庭的特发性震颤有关。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-05-26 DOI: 10.1007/s10048-025-00827-6

Bin Wang, Bin Wei, Likui Lu, Sha Liu, Wei Ge, Miao Sun

{"title":"A heterozygous variation of PINK1 is potentially associated with essential tremor in a Chinese family.","authors":"Bin Wang, Bin Wei, Likui Lu, Sha Liu, Wei Ge, Miao Sun","doi":"10.1007/s10048-025-00827-6","DOIUrl":"https://doi.org/10.1007/s10048-025-00827-6","url":null,"abstract":"Essential tremor (ET) is a common movement disorder, but its pathophysiologic mechanisms remain elusive. So far, a few genes/loci have been identified, but because of genetic heterogeneity, the genetic etiology of ET is still one of the main challenges. In this study, we report an autosomal dominant ET Chinese pedigree in which the patients presented with involuntary tremor of the head or upper limbs, with a slow progression of symptoms, no difficulty in starting and turning, no slow walking, no other significant findings were noted on neurological examination. A heterozygous missense mutation (c.158G > A, p.G53D) in PINK1 (PTEN-induced kinase 1) was identified by whole-exome sequencing of four affected individuals from this ET family. Confirmed by Sanger sequencing, we find that this PINK1 missense variant co-segregate with ET phenotypes in this pedigree with all the affected subjects, showing clear genotype-phenotype correlation. In addition, the new missense mutation was functionally analyzed by western blotting and mitochondrial membrane potential assay after cell transfection. It was found that PINK1 may play a protective role for cells, whereas the c.158G > A (p.G53D) missense mutation leads to a loss of cellular protection, thereby increasing cellular sensitivity to stress. Thus, this study provides a heterozygous missense mutation in PINK1 potentially associated with ET.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"45"},"PeriodicalIF":1.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of mutations in five Pakistani families with Epilepsy. 五个巴基斯坦癫痫家族的突变鉴定。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-05-19 DOI: 10.1007/s10048-025-00824-9

Nayab Ahsan, Arsalan Ahmad, Shahnawaz Hussain, Nasreen Fatima, Imran Khan Yousafzai, Umm-E- Kalsoom, Rubina Dad, Muhammad Jawad Hassan

{"title":"Identification of mutations in five Pakistani families with Epilepsy.","authors":"Nayab Ahsan, Arsalan Ahmad, Shahnawaz Hussain, Nasreen Fatima, Imran Khan Yousafzai, Umm-E- Kalsoom, Rubina Dad, Muhammad Jawad Hassan","doi":"10.1007/s10048-025-00824-9","DOIUrl":"https://doi.org/10.1007/s10048-025-00824-9","url":null,"abstract":"Epilepsy is a group of neurological conditions characterized by epileptic seizures, which are episodes that may vary from brief and nearly undetectable to long periods of vigorous shaking. Due to high rates of close family marriages (consanguinity) in the Pakistani population, families with multiple affected individuals showing novel or known epilepsy phenotypes are likely to present. The present study aimed to identify the genetic causes of epileptic conditions (isolated or syndromic) in selected families. For this purpose, five families (A-E) with multiple affected individuals showing a form of epilepsy were recruited after thorough clinical investigations. Next Generation Sequencing (NGS) based gene panel testing was applied to identify the pathogenic variants in these families. DNA samples of one affected individual from each family were sent to a renowned genetic testing lab (Invitae, USA) for Epilepsy Comprehensive Gene Panel Testing. Bioinformatics (SIFT, PolyPhen2) tools were used to validate the pathogenicity of identified mutations. We identified five previously reported mutations in these five families; all of them were predicted to be pathogenic by bioinformatics analysis. The findings would certainly help enhance our understanding regarding the etiology of inherited epilepsies and would facilitate genetic counseling and clinical management in these families.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"44"},"PeriodicalIF":1.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic variants associated with idiopathic Parkinson's disease in Latin America: A systematic review. 拉丁美洲与特发性帕金森病相关的遗传变异：一项系统综述

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-04-03 DOI: 10.1007/s10048-025-00817-8

Felipe Duarte-Zambrano, David Felipe Alfonso-Cedeño, Jorge A Barrero, Luis Alejandro Rodríguez-Vanegas, Valentina Moreno-Cárdenas, Anamaría Olarte-Díaz, Gonzalo Arboleda, Humberto Arboleda

{"title":"Genetic variants associated with idiopathic Parkinson's disease in Latin America: A systematic review.","authors":"Felipe Duarte-Zambrano, David Felipe Alfonso-Cedeño, Jorge A Barrero, Luis Alejandro Rodríguez-Vanegas, Valentina Moreno-Cárdenas, Anamaría Olarte-Díaz, Gonzalo Arboleda, Humberto Arboleda","doi":"10.1007/s10048-025-00817-8","DOIUrl":"10.1007/s10048-025-00817-8","url":null,"abstract":"Idiopathic Parkinson's disease (PD) constitutes a complex trait influenced by genetic, environmental, and lifestyle factors, with an estimated heritability of nearly 30%. However, a large proportion of the heritable variation linked to PD remains uncertain, partly due to ancestral bias. Expanding research into Hispanic populations can contribute to address this gap. To review the evidence of genetic variants associated with idiopathic PD in Latin America. A PRISMA-compliant systematic review was conducted in MEDLINE, EMBASE and LILACS, compiling studies published up to February 7, 2025. Nineteen case-control studies were included. Two hypothesis-free studies identified rs525496 near H2BW1 as a protective factor and rs356182 in SNCA as a risk factor through XWAS and GWAS, respectively. Seventeen hypothesis-driven studies examined over three hundred variants, identifying nineteen genetic markers; risk factors included one INDEL in NR4A2, CNV burdens in PRKN, SNCA, and PLA2G6, along with fourteen variants in six loci including GBA, APOEε4, MTHFR, LRRK2, and SNCA. Three SNPs in the PICALM, ALDH1A1, and APOE-ε3 loci were identified as protective factors. Additionally, six SNCA variant haplotypes appear to increase PD risk, while two NR4A2 INDELs haplotypes showed mixed effects. This review summarized genetic loci associated with idiopathic PD in Latin American populations evidencing an overlap with European findings as well as novel loci, although awaiting replication and validation. These observations contribute to the understanding of genetic configuration of the disease and highlight the need for further genomic research in underrepresented groups that include local ancestry analysis within admixed cohorts to guide development of personalized treatments and population-specific interventions.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"43"},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel FBXW11 variant in a patient with neurodevelopmental, jaw, eye, and digital syndrome. 神经发育、颌、眼和指综合征患者的新型FBXW11变异

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-04-03 DOI: 10.1007/s10048-025-00822-x

Anna Maznina, Daria Molodtsova-Zolotukhina, Nina Andreeva, Anton Esibov, Fatima M Bostanova, Artem Sharkov, Natalya A Doroshchuk, Olesya V Sagaydak, Olga S Groznova, Mary Woroncow, Viktor P Bogdanov, Pavel Y Volchkov

{"title":"A novel FBXW11 variant in a patient with neurodevelopmental, jaw, eye, and digital syndrome.","authors":"Anna Maznina, Daria Molodtsova-Zolotukhina, Nina Andreeva, Anton Esibov, Fatima M Bostanova, Artem Sharkov, Natalya A Doroshchuk, Olesya V Sagaydak, Olga S Groznova, Mary Woroncow, Viktor P Bogdanov, Pavel Y Volchkov","doi":"10.1007/s10048-025-00822-x","DOIUrl":"10.1007/s10048-025-00822-x","url":null,"abstract":"Neurodevelopmental, jaw, eye, and digital syndrome (NEDJED) is a rare autosomal dominant condition that has demonstrated diverse phenotypes. This is the second case report published on this condition, covering the disease history of an 8 year old patient with a severe manifestation of the disease. The patient was born with hydrocephalus, and demonstrated major developmental delay as he aged. Whole-genome sequencing of the patient and his parents was conducted, detecting a de novo variant, NM_001378974.1:c.1220 A > T [p.Lys407Ile], located in the conserved WD4 region of the WD40 domain of FBXW11, which is consistent with all previously reported patients. The phenotype of the patient is presented with a focus on MRI and EEG features, including images and detailed description for both. While the patient's phenotype is overall consistent with previous findings, there are a number of major factors we believe are caused by the FBXW11 variant that have not been previously described, such as the patient's complete inability to walk.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"41"},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The association of SCN1A polymorphisms with epilepsy and drug resistance: a systematic review and meta-analysis. SCN1A多态性与癫痫和耐药的关联：一项系统综述和荟萃分析。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-04-03 DOI: 10.1007/s10048-025-00823-w

Ida Mohammadi, Shahryar Rajai Firouzabadi, Aryan Aarabi, Samin Sadraei, Aidin Saadati, Sana Mohammad Soltani, Behnam Safarpour Lima

{"title":"The association of SCN1A polymorphisms with epilepsy and drug resistance: a systematic review and meta-analysis.","authors":"Ida Mohammadi, Shahryar Rajai Firouzabadi, Aryan Aarabi, Samin Sadraei, Aidin Saadati, Sana Mohammad Soltani, Behnam Safarpour Lima","doi":"10.1007/s10048-025-00823-w","DOIUrl":"10.1007/s10048-025-00823-w","url":null,"abstract":"Epilepsy is one of the most common neurological afflictions worldwide, with one-third of patients exhibiting resistance to treatment. It has been speculated that the polymorphisms of the sodium channel alpha subunit 1 (SCN1A) gene are associated with both the occurrence of epilepsy and its resistance to treatment. The aim of this study is to systematically review the literature and conduct meta-analyses revealing the associations of the SCN1A polymorphisms with epilepsy and resistance to treatment. We conducted a search of Pubmed, Web of Science, and Scopus, and if more than two studies investigated a polymorphism, odds ratios for association with epilepsy and/or resistance to treatment were calculated in three allelic, homozygous, and recessive genetic models. The initial search yielded 4106 items, and a total of 64 articles met the final inclusion criteria. With respect to the occurrence of epilepsy, the rs2298771 polymorphism was revealed to be negatively associated in the recessive model, while the associations of other polymorphisms were not statistically significant. With regard to resistance to treatment, rs2298771 was revealed to be positively associated across all three models, and rs10167228 was positively associated in the allelic and homozygous models, but not the recessive model. Other polymorphisms were not shown to be associated with resistance to treatment. In conclusion, we demonstrated that the rs2298771 polymorphism had a significant and negative association with the occurrence of epilepsy. Furthermore, rs2298771 and rs10167228 polymorphisms had positive associations with resistance to treatment. Further studies are needed to explore these associations among other polymorphisms.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"42"},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systematic review of hereditary neurological disorders diagnosed by whole exome sequencing in Pakistani population: updates from 2014 to November 2024. 巴基斯坦人群全外显子组测序诊断的遗传性神经疾病的系统综述：2014年至2024年11月的最新情况。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-04-03 DOI: 10.1007/s10048-025-00819-6

Riaz Ahmad, Muhammad Naeem

{"title":"A systematic review of hereditary neurological disorders diagnosed by whole exome sequencing in Pakistani population: updates from 2014 to November 2024.","authors":"Riaz Ahmad, Muhammad Naeem","doi":"10.1007/s10048-025-00819-6","DOIUrl":"10.1007/s10048-025-00819-6","url":null,"abstract":"Hereditary neurological disorders (HNDs) are a group of heterogeneous disorders characterized by significant genetic and clinical variability. HNDs are caused by dysfunction of the central or peripheral nervous system due to aberrant electrical impulses. More than 600 types of HNDs have been documented, and overall, these are the second leading cause of death worldwide. This systematic review is based on a retrospective analysis of research articles reporting HNDs diagnosed using whole exome sequencing in Pakistani families from 2014 to November 2024. Original research articles were retrieved through online surveys, notably Google Scholar, PubMed, and the Web of Science. Based on stringent selection criteria, 89 research articles and 188 variants published around 10 years were considered. Variants and research articles were cross-checked and further validated in different online databases/resources to confirm their genomic nomenclature and pathogenicity according to the ACMG guidelines. A total of 188 variants in 143 distinct genes in Pakistani families identified through whole exome sequencing have been reported to date that caused genetic and clinically heterogeneous HNDs. Consanguineous parentage was found in around 90% of cases, and approximately 91% of causative alleles were reported in homozygous state showing a predominant burden of HNDs because of blood-related marriages. The most frequent type of pathogenic variants were single nucleotide substitutions (92 missense and 39 nonsense). Among 188 variants, 76 variants were reported in 2024 and 44 variants were observed in 2023. Pakistan is the fifth most populous country in the world having an extreme prevalence of consanguinity resulting in the expression of pathogenic variants due to homozygosity. Therefore, there is a prevalence of genetic disorders particularly rare monogenic or Mendelian disorders. Next-generation sequencing approach is strongly recommended for diagnosis, early therapeutic intervention and genetic counselling.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"40"},"PeriodicalIF":1.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-target approach to Alzheimer's disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms. 阿尔茨海默病预防和治疗的多靶点方法：抗氧化、抗炎和淀粉样蛋白调节机制。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-04-01 DOI: 10.1007/s10048-025-00821-y

Kashif Abbas, Mohd Mustafa, Mudassir Alam, Safia Habib, Waleem Ahmad, Mohd Adnan, Md Imtaiyaz Hassan, Nazura Usmani

{"title":"Multi-target approach to Alzheimer's disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms.","authors":"Kashif Abbas, Mohd Mustafa, Mudassir Alam, Safia Habib, Waleem Ahmad, Mohd Adnan, Md Imtaiyaz Hassan, Nazura Usmani","doi":"10.1007/s10048-025-00821-y","DOIUrl":"10.1007/s10048-025-00821-y","url":null,"abstract":"Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation, neurofibrillary tangles, neuroinflammation, and progressive cognitive decline, posing a significant global health challenge. Growing evidence suggests that dietary polyphenols may reduce the risk and progression of AD through multifaceted neuroprotective mechanisms. Polyphenols regulate amyloid proteostasis by inhibiting β/γ-secretase activity, preventing Aβ aggregation, and enhancing clearance pathways. Their strong antioxidant properties neutralize reactive oxygen species, chelate redox-active metals, and activate cytoprotective enzymes via Nrf2 signaling. This review examines the potential therapeutic targets, signaling pathways, and molecular mechanisms by which dietary polyphenols exert neuroprotective effects in AD, focusing on their roles in modulating amyloid proteostasis, oxidative stress, neuroinflammation, and cerebrovascular health. Polyphenols mitigate neuroinflammation by suppressing NF-κB signaling and upregulating brain-derived neurotrophic factor, supporting neuroplasticity and neurogenesis. They also enhance cerebrovascular health by improving cerebral blood flow, maintaining blood-brain barrier integrity, and modulating angiogenesis. This review examines the molecular and cellular pathways through which polyphenols exert neuroprotective effects, focusing on their antioxidant, anti-inflammatory, and amyloid-modulating roles. We also discuss their influence on key AD pathologies, including Aβ deposition, tau hyperphosphorylation, oxidative stress, and neuroinflammation. Insights from clinical and preclinical studies highlight the potential of polyphenols in preventing or slowing AD progression. Future research should explore personalized dietary strategies that integrate genetic and lifestyle factors to optimize the neuroprotective effects of polyphenols.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"39"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial DNA variants revealed by whole exome sequencing: from screening to diagnosis and follow-up. 全外显子组测序揭示的线粒体DNA变异：从筛查到诊断和随访。

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-03-26 DOI: 10.1007/s10048-025-00820-z

Sebastian Skoczylas, Tomasz Płoszaj, Karolina Gadzalska, Monika Gorządek, Paulina Jakiel, Ewa Juścińska, Maria Malarska, Magdalena Traczyk-Borszyńska, Hanna Biezynska, Magdalena Rychlik, Agata Pastorczak, Agnieszka Zmysłowska

{"title":"Mitochondrial DNA variants revealed by whole exome sequencing: from screening to diagnosis and follow-up.","authors":"Sebastian Skoczylas, Tomasz Płoszaj, Karolina Gadzalska, Monika Gorządek, Paulina Jakiel, Ewa Juścińska, Maria Malarska, Magdalena Traczyk-Borszyńska, Hanna Biezynska, Magdalena Rychlik, Agata Pastorczak, Agnieszka Zmysłowska","doi":"10.1007/s10048-025-00820-z","DOIUrl":"10.1007/s10048-025-00820-z","url":null,"abstract":"Mutations in mitochondrial DNA play a crucial role in several diseases, but interpreting the clinical significance of mitochondrial DNA variants is challenging due to heteroplasmy, age-related loss of variants and evolving phenotypes. The aim of study was to identify mitochondrial pathogenic variants and explore their potential future association with specific phenotypes in patients during their lifetime, for both known and novel variants. We used a Python pipeline to analyse exome sequencing data from 418 patients (median age: 15 years; 52.9% males and 47.1% females), mostly diagnosed with neurological disorders, developmental and intellectual disabilities, behavioural and sensory disorders, cardiovascular and metabolic abnormalities, renal diseases and others. Screening identified 1,000 unique variants with heteroplasmy levels greater than 10% and 192 unique variants with 1-10% heteroplasmy, excluding hypervariable regions. Among these variants, four confirmed pathogenic variants were detected according to MITOMAP (m.1555 A > G, m.3243 A > G, m.9035T > C, and m.11778G > A), each identified in one patient. The application of pathogenicity and frequency criteria led to the identification of three unique variants and one in monozygotic twin sister with low levels of heteroplasmy, which were confirmed by next-generation sequencing. Finally, one of them, the variant m.15897G > A, was recognised as likely pathogenic (PP3, PS2). Our study highlights the complexity of diagnosing mitochondrial diseases associated with mtDNA mutations and emphasises the need for a comprehensive genotype-phenotype approach to correctly identify causal variants.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"38"},"PeriodicalIF":1.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repeated clear benefits of immunotherapy in a patient with Charcot-Marie-Tooth disease carrying a rare point mutation in PMP22. 携带PMP22罕见点突变的腓骨肌萎缩症患者免疫治疗的反复明确益处

IF 1.6 4区医学

Neurogenetics Pub Date : 2025-03-24 DOI: 10.1007/s10048-025-00808-9

Honami Kawai, Yoichiro Nishida, Takashi Kanda, Takanori Yokota

引用次数: 0