Neurogenetics最新文献

{"title":"Moyamoya disease presenting with transient nonfocal neurological attacks in an Indian woman carrying a previously unreported RNF213 missense variant (p.Thr554Ile).","authors":"Ritwick Mondal, Shramana Deb, Nirmalya Ray, Sukalyan Purakayastha, Mona Tiwari, Julián Benito-León, Jayanta Roy","doi":"10.1007/s10048-025-00836-5","DOIUrl":"https://doi.org/10.1007/s10048-025-00836-5","url":null,"abstract":"<p><p>Moyamoya disease is a rare cerebrovascular disorder characterized by progressive internal carotid artery stenosis and compensatory collateral vessel formation, producing a characteristic \"puff of smoke\" angiographic appearance. Genetic predisposition, particularly involving the RNF213 gene, plays a central role. We report a 48-year-old Indian woman with type 2 diabetes, arterial hypertension, and a prior transient ischemic attack who presented with intermittent bilateral upper limb paresthesia. Imaging revealed bilateral supraclinoid internal carotid artery stenosis (Suzuki stage III). Genetic testing identified a heterozygous RNF213 missense variant (Thr554Ile, rs766831703), which is extremely rare in global databases and predicted to be deleterious by multiple in silico tools. This variant has not been previously described in association with Moyamoya disease. The patient underwent bilateral superficial temporal artery to middle cerebral artery bypass, achieving sustained clinical improvement without recurrent events over two years.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"54"},"PeriodicalIF":1.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669091","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}

{"title":"Complete commissural agenesis in a child with Noonan-like syndrome with loose anagen hair 2.","authors":"Simone Gana, Luisa Piccinni, Elisa Rognone, Alessia Beverino, Costanza Varesio, Alessia Asaro, Anna Pichiecchio, Enza Maria Valente","doi":"10.1007/s10048-025-00832-9","DOIUrl":"10.1007/s10048-025-00832-9","url":null,"abstract":"<p><p>RASopathies are a wide group of multisystemic disorders caused by pathogenic variants in genes belonging to the RAS/MAPK pathway. Among these, PPP1CB gene variants cause Noonan syndrome-like disorder with loose anagen hair 2 (NSLAH2), a rare condition with neuro-cardio-facio-skeletal involvement and the peculiar loose anagen hair. We report on a girl carrying the recurrent c.146 C > G (p.Pro49Arg) pathogenic variant, who presented the classical NSLH features associated with a previously unreported complete commissural agenesis, likely expanding the phenotype. The prominent role of Ras protein in oligodendrocyte maturation and differentiation might lend biological plausibility to the myelination impairment observed in our patient.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"53"},"PeriodicalIF":1.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531297","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}

{"title":"Experience in the clinical and genetic diagnosis of a series of Algerian patients with hereditary spastic paraplegias.","authors":"Mouna Messaoud-Khelifi, Razika Boulariah-Hadjou, Mohamed Islam Kediha, Lena Guillot-Noel, Marine Guillaud-Bataille, Christelle Marie Durand, Lamia Ali-Pacha, Wahiba Amer El Khedoud, Fanny Mochel, Jean-Madeleine de Sainte-Agathe, Giovanni Stevanin","doi":"10.1007/s10048-025-00833-8","DOIUrl":"https://doi.org/10.1007/s10048-025-00833-8","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"52"},"PeriodicalIF":1.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487242","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}

{"title":"Identification of a de Novo MARK2 gene variant in a patient with autism spectrum disorder, epilepsy, and neurodevelopmental delay.","authors":"Xiaolan Sun, Yong Chen, Jianmin Zhong, Hui Chen, Jihua Xie, Ruiyan Wang","doi":"10.1007/s10048-025-00831-w","DOIUrl":"10.1007/s10048-025-00831-w","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition that is frequently accompanied by developmental delay and epilepsy. There is increasing evidence that genetic factors play a key role and that variations in the MARK2 gene are associated with neurodevelopmental disorders. Nevertheless, clinical reports associating MARK2 variants with human disease remain limited. Exome sequencing (ES) was performed on a patient with ASD, developmental delay, and epilepsy. Candidate variants were prioritized based on inheritance patterns, population allele frequency, and clinical relevance, following the ACMG guidelines. Sanger sequencing was used to validate the identified variant in the family. The patient is a five-year-old male who presented with ASD, epilepsy and developmental delay. The brain MRI was normal, but the EEG results showed abnormal brain activity with sharp and slow waves in the right occipital and posterior temporal regions. A frameshift variant in the MARK2 (c.645_646insA, p.(Ala216Serfs*12)) gene was identified in the patient through ES. It was de novo and confirmed by Sanger sequencing. This study contributes to the expansion of the genotypic spectrum of MARK2-related neurodevelopmental disorders. A novel de novo frameshift variant was identified in a patient with ASD, developmental delay and epilepsy. These findings provide further evidence supporting the role of MARK2 as a disease-associated gene and highlight its potential role in neurodevelopment.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"51"},"PeriodicalIF":1.6,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340744","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}

{"title":"Strabismus and nystagmus in oculocutaneous albinism: clinical perspectives, diagnosis, and role of neurotransmitters.","authors":"Vaishali Dobhal, Ashwani Kumar, Ishu Garg, Aman Kumar, Falguni Goel","doi":"10.1007/s10048-025-00830-x","DOIUrl":"https://doi.org/10.1007/s10048-025-00830-x","url":null,"abstract":"<p><p>The rare recessive autosomal non-communicable disorder oculocutaneous albinism causes discoloration of the eye, hair, and skin. Oculocutaneous albinism is a hereditary group of disorders with sub-differential characteristics like reduction of pilar, cutaneous, and ocular pigmentation. Clinical characteristics and symptoms include strabismus, iris hypopigmentation, nystagmus, reduced visual acuity, foveal hypoplasia, refractive errors, photophobia, and colour-visual impairment. The associated genetic mutation results in the reduced activity of tyrosine activity required for the metabolism of melanin further. Genes that are majorly involved in different types of oculocutaneous albinism (OCA) are the TYR, MATP, SLC24A5, TYRP1, and SLCA5A2. Also, gene sequences LYST and HPS1 account for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome, respectively, which have clinical symptoms of OCA. The exact gene mutation can be understood by various methods of a diagnostic approach, like denaturing high-performance liquid chromatography and sequential analysis that involves computational techniques. The most prevalent form of albinism, OCA1, is associated with a mutational defect in the TYR gene. Further, neuromodulators like GABA, acetylcholine, and dopamine are responsible for retinal abnormality and dysregulation, exacerbating the oculocutaneous albinism. Understanding all these genetic mutations and neurotransmitter deficiencies will help in generating the targeted gene and other drug delivery systems.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"50"},"PeriodicalIF":1.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327873","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}

{"title":"Phenotypic variability and preserved cognition in a family with KCNA2-related developmental epileptic encephalopathy.","authors":"Arastoo Kaki, Maedeh Ganji, Mohammad Farid Mohammadi, Fatemeh Bahreini, Mojtaba Movahedinia, Reena G Rastogi, Pouria Mohammadi, Ali Reza Tavasoli","doi":"10.1007/s10048-025-00829-4","DOIUrl":"10.1007/s10048-025-00829-4","url":null,"abstract":"<p><p>Developmental and epileptic encephalopathy type 32 (DEE32) is a severe neurological disorder caused by pathogenic variants in the KCNA2 gene, encoding the Kv1.2 voltage-gated potassium channel. DEE32 typically presents with early-onset seizures, ataxia, and intellectual impairment, though severity varies widely. We describe a family with a rare KCNA2 loss-of-function variant in two siblings, evaluating their clinical phenotype, neuroimaging, electroencephalography (EEG), developmental assessments, and treatment response. Cognitive function in patients 1 and 2 was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), while cognitive function in patient 3 was inferred from his ability to maintain employment and function independently. The family included a father and two children, all with early-onset seizures in infancy and normal development. Patient 1, a male, exhibited delayed myelination at 15 months, with seizures initially controlled but later recurring after medication weaning. His WPPSI assessment indicated normal cognition with a standard score of 113, and his mild speech delay resolved. Patient 2, a female, had a normal brain MRI and normal WPPSI evaluation (standard score of 111), with well-controlled seizures on zonisamide. The father had childhood-onset epilepsy persisting into adulthood, ultimately leading to Sudden Unexpected Death in Epilepsy (SUDEP) at age 30. Genetic testing confirmed that both children carried the c.765_773del (p.Met255_Ile257del) KCNA2 variant, linking their seizures to the father's epilepsy. Patients 1 and 2 responded well to zonisamide, while patient 3's response remains unknown due to a lack of medical records. This study highlights the variability of KCNA2-related epilepsy, ranging from early-onset seizures to long-term epilepsy with developmental delays and episodic ataxia. Despite carrying a loss-of-function variant, both children demonstrated a favorable response to zonisamide without additional neurological manifestations. Our findings underscore the need for further research into genetic modifiers of KCNA2 phenotypes. The interpretation of any association between SUDEP and KCNA2-related epilepsy and the determination of cause of death is hampered by limited data, as it is based on a single case with normal cardiac evaluation.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"49"},"PeriodicalIF":1.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295466","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}

{"title":"Zebrafish as a tool for autism research: unraveling the roles of Shank3, Cntnap2, Neuroligin3, and Arid1b in synaptic and behavioral abnormalities.","authors":"Akansha Pal, Falguni Goel, Vipin Kumar Garg","doi":"10.1007/s10048-025-00828-5","DOIUrl":"https://doi.org/10.1007/s10048-025-00828-5","url":null,"abstract":"<p><p>Autism Spectrum Disorder, a complex neurodevelopmental disorder, is manifested by deficits in social communication and restricted, repetitive patterns of behavior, interests, or activities. Its molecular mechanism of pathology is not that much understood, though various genetic mutations have been established in its causation. The most important genes are Shank3, Cntnap2, Neuroligin3, and Arid1b. Recently, zebrafish (Danio rerio) have emerged as a highly valuable model organism to study these genetic contributions to ASD, given their genetic tractability, transparent embryos, and ease of behavioral assessment. This review discusses the models of zebrafish used to examine the roles of Shank3, Cntnap2, Neuroligin3, and Arid1b in synaptic function, neuronal connectivity, and behavioral abnormalities characteristic of ASD. We discuss the molecular pathways affected by mutations in these genes, including synapse formation, excitatory/inhibitory balance, and neuronal signaling, which lead to the neurodevelopmental impairments observed in ASD. We have also highlighted the various behavioral assays in zebrafish, such as social interaction tests, sensory processing assays, and repetitive behavior measurements, which are used to study ASD-like phenotypes. The unique advantages of zebrafish include high-throughput potential, the ability to monitor real-time neuronal activity, and the ease with which genetic manipulations can be done. The review focuses on the advancement of zebrafish in understanding ASD and their potential for rising targeted interventions to address core symptoms of the disorder.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"48"},"PeriodicalIF":1.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236064","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}

{"title":"A case series of joubert syndrome evaluated with whole exome sequencing and the utility of optical genome mapping in the diagnosis.","authors":"Aslihan Kiraz, Murat Erdogan, Burhan Balta, Hakan Gumus, Mehmet Burak Mutlu, Nurana Mammadova, Firat Ozcelik, Izem Olcay Sahin, Ahmet Sami Guven, Sefer Kumandas, Ahmet Savranlar, Filiz Karaman, Huseyin Per, Munis Dundar","doi":"10.1007/s10048-025-00825-8","DOIUrl":"https://doi.org/10.1007/s10048-025-00825-8","url":null,"abstract":"<p><strong>Background: </strong>Joubert syndrome (JS) is a rare autosomal recessive genetic disease characterized by molar tooth sign, hypotonia during infancy, developmental delay, and/or intellectual disability. Over 40 genes have been associated with the syndrome, and population-specific founder variants have been defined.</p><p><strong>Methods: </strong>In our study, we evaluated 34 patients with clinical, radiological, and laboratory findings. Whole exome sequencing (WES) analysis was performed on all patients to explain the underlying genetic causes. Optical genome mapping (OGM) was performed to elucidate the genetic mechanism in two patients with heterozygous variants after WES analysis.</p><p><strong>Results: </strong>Eighteen homozygous, three compound heterozygous, and two heterozygous variants were present in thirteen patients. AHI1, c.961dupG, p.Asp321fs*5; CPLANE1, c.569A > G, p.Glu190Gly; CPLANE1, c.7495dup, Ile2499Asnfs*2; CC2D2A, c.4143G > T, p.Lys1381Asn; KIAA0586, c.4889 T > C, p.Leu1630Pro; PIBF1, c.1231C > T, p.Arg411Ter; TMEM237, c.591delG, p.Thr198Profs*5; TMEM138, c.376G > C, p.Ala126Pro were novel variants. In addition, in the OGM analysis, a heterozygous insertion was detected in the 3'UTR region of RPGRIP1L. Patients with a diagnosis of JS that could not be explained by WES itself but could be explained together with OGM were discussed.</p><p><strong>Conclusion: </strong>This study contributes to the clinical and molecular characteristics of JS patients. Despite growing literature about JS, this is the first study to use OGM for the diagnosis.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"47"},"PeriodicalIF":1.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192540","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}

{"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":"10.1007/s10048-025-00826-7","url":null,"abstract":"<p><p>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.</p>","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}

{"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":"10.1007/s10048-025-00827-6","url":null,"abstract":"<p><p>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.</p>","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}