Neurogenetics最新文献_第3页

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-22 DOI: 10.1007/s10048-024-00780-w

Álvaro de Oliveira Franco, Matheus Bernardon Morillos, Martim Tobias Bravo Leite, Marino Muxfeldt Bianchin, Carolina Machado Torres

引用次数: 0

Expansion of phenotypic and genotypic data in autism spectrum disorders due to variants in the CHD8 gene. 自闭症谱系障碍的表型和基因型数据因 CHD8 基因变异而扩大。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-22 DOI: 10.1007/s10048-024-00781-9

Mariia A Parfenenko, Ilya S Dantsev, Sergei V Bochenkov, Rabiat G Kuramagomedova, Natalia V Vinogradova, Mariia P Afanaseva, Olga S Groznova, Victoria Iu Voinova

{"title":"Expansion of phenotypic and genotypic data in autism spectrum disorders due to variants in the CHD8 gene.","authors":"Mariia A Parfenenko, Ilya S Dantsev, Sergei V Bochenkov, Rabiat G Kuramagomedova, Natalia V Vinogradova, Mariia P Afanaseva, Olga S Groznova, Victoria Iu Voinova","doi":"10.1007/s10048-024-00781-9","DOIUrl":"10.1007/s10048-024-00781-9","url":null,"abstract":"Autism spectrum disorders are a group of the most common disorders of neuropsychiatric development, characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns. This group of conditions frequently co-occurs with intellectual disability, epilepsy, attention-deficit hyperactivity disorder, connective tissue disorders and others. Among the most common molecular-genetic causes of autism spectrum disorders are pathogenic variants in the CHD8 gene. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and brain development in embryogenesis. 6 children and 1 adult (mother of 1 of the children) and were found to have clinically significant variants in CHD8 on whole genome sequencing (3 children and 1 adult had likely pathogenic variants, 3 children- variants of unknown significance). Their phenotype consisted of autism spectrum disorders, developmental delay, ataxia, overgrowth and other signs typically observed in patients with pathogenic variants in CHD8, as well as common comorbidities of autism spectrum disorders, such as attention-deficit hyperactivity disorder and connective tissue disorders. Additionally, 4 patients had hepatomegaly and 2- hyperbilirubinemia (1 had both) - clinical features have not been previously associated with pathogenic variants in CHD8. 2 patients also presented with cardiovascular abnormalities, primarily arrythmias and, in 1 case, cardiomyopathy- also uncharacteristic of patients with pathogenic variants in CHD8. Further research is required to determine the mechanisms underlying the abovementioned clinical features, which are likely carried out through complex interactions between CHD8 and other regulatory proteins.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"4"},"PeriodicalIF":1.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689694","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

Dystrophinopathy patient data as a guide to interpretation of pregestational female population screening for DMD gene variants. 以肌营养不良症患者数据为指导，解读孕前女性人群 DMD 基因变异筛查。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-20 DOI: 10.1007/s10048-024-00788-2

Lena Sagi-Dain, Annemieke Aartsma-Rus, Moran Echar, Julia Grinshpun-Cohen, Amihood Singer

{"title":"Dystrophinopathy patient data as a guide to interpretation of pregestational female population screening for DMD gene variants.","authors":"Lena Sagi-Dain, Annemieke Aartsma-Rus, Moran Echar, Julia Grinshpun-Cohen, Amihood Singer","doi":"10.1007/s10048-024-00788-2","DOIUrl":"10.1007/s10048-024-00788-2","url":null,"abstract":"Pregestational population screening of healthy females for copy number variants in DMD gene has raised numerous challenges regarding the interpretation and disclosure of these findings. Our objective was to analyze data from a local dystrophinopathy patient database, in comparison to population screening results. Utilizing the \"Little steps\" association registry for children with dystrophinopathy, we classified genetic findings (out-of-frame, in-frame, or difficult-to-predict) in 231 DMD and 90 BMD male patients. A comparison was made with a previously published cohort of 162 female carriers identified through population screening. Duplications classified as \"difficult to predict\" were absent in DMD/BMD patients, as opposed to 45.1% of women analyzed in the scope of population screening (p < 0.0001). While the distribution of deletions did not differ between the groups, significantly higher proportion of duplications initiated at the proximal hot spot in the DMD/BMD cohort (87.1%), vs. only 11.7% in women analyzed through population screening (p = 0.0038). Notably, duplications initiating in the dp427c promoter area were noted only in the latter cohort (n = 62). Local databases of dystrophinopathy patients can facilitate analysis and reporting of pregestational female population screening results. These conclusions facilitate future introductions of population screening genetic tests for diseases with variable presentation.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"2"},"PeriodicalIF":1.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677853","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

Introducing a novel TRAPPC10 gene variant as a potential cause of developmental delay and intellectual disability in an Iranian family. 引入一种新型 TRAPPC10 基因变异，作为一个伊朗家庭中发育迟缓和智力残疾的潜在原因。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-11-19 DOI: 10.1007/s10048-024-00785-5

Ahoura Nozari, Paria Babaahmadi, Narges Jalilian, Taha Sadeghi, Mahdieh Hasani

{"title":"Introducing a novel TRAPPC10 gene variant as a potential cause of developmental delay and intellectual disability in an Iranian family.","authors":"Ahoura Nozari, Paria Babaahmadi, Narges Jalilian, Taha Sadeghi, Mahdieh Hasani","doi":"10.1007/s10048-024-00785-5","DOIUrl":"10.1007/s10048-024-00785-5","url":null,"abstract":"Background: TRAPP complexes are crucial components for intracellular transport and cellular organization. Their role in vesicle trafficking, particularly through their involvement in the secretory pathway, make them more important in neurodevelopmental mechanisms. This study aims to identify a novel genetic variant, associated with developmental delay and intellectual disability by analyzing a consanguineous Iranian family.Materials and methods: Here, we performed whole-exome sequencing on an Iranian family, originating from a small population. The patient presented with severe developmental delay, microcephaly, and behavioral abnormalities. Through our analysis, we discovered a new biallelic variant on a previously introduced gene: TRAPPC10 (NM_003274.5): c.3222 C > A; p.(Cys1074Ter) that is a potential cause for these specific clinical characteristics.Results: Previous functional analysis suggest that the mutation causes premature termination of protein translation, likely leading to nonsense-mediated decay because of biallelic loss of functional TRAPPC10 protein which leads to severe developmental delay, microcephaly, and behavioral abnormalities such as aggression and autistic traits.Conclusion: The aim of this research is to discover a novel variant in the TRAPPC10 gene that is responsible for a particular neurodevelopmental condition, dominantly characterized by developmental delay, intellectual disability, and microcephaly. These findings advance the comprehension of TRAPP-related diseases and emphasize the need for further exploration into the impact of TRAPPC10 on the development of the nervous system.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"1"},"PeriodicalIF":1.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670037","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

Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy. Kufor-Rakeb 综合征相关性精神病：一种新型功能缺失 ATP13A2 变异和对抗抑郁治疗的反应。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-10-01 Epub Date: 2024-07-18 DOI: 10.1007/s10048-024-00767-7

Mark Ainsley Colijn, Stephanie Vrijsen, Ping Yee Billie Au, Rania Abou El Asrar, Marine Houdou, Chris Van den Haute, Justyna Sarna, Greg Montgomery, Peter Vangheluwe

{"title":"Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy.","authors":"Mark Ainsley Colijn, Stephanie Vrijsen, Ping Yee Billie Au, Rania Abou El Asrar, Marine Houdou, Chris Van den Haute, Justyna Sarna, Greg Montgomery, Peter Vangheluwe","doi":"10.1007/s10048-024-00767-7","DOIUrl":"10.1007/s10048-024-00767-7","url":null,"abstract":"Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"405-415"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635966","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

Spinocerebellar ataxia type 27B (SCA27B) in India: insights from a large cohort study suggest ancient origin. 印度的脊髓小脑共济失调 27B 型 (SCA27B)：一项大型队列研究揭示了其古老的起源。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI: 10.1007/s10048-024-00770-y

Tiyasha De, Pooja Sharma, Bharathram Upilli, A Vivekanand, Shreya Bari, Akhilesh Kumar Sonakar, Achal Kumar Srivastava, Mohammed Faruq

{"title":"Spinocerebellar ataxia type 27B (SCA27B) in India: insights from a large cohort study suggest ancient origin.","authors":"Tiyasha De, Pooja Sharma, Bharathram Upilli, A Vivekanand, Shreya Bari, Akhilesh Kumar Sonakar, Achal Kumar Srivastava, Mohammed Faruq","doi":"10.1007/s10048-024-00770-y","DOIUrl":"10.1007/s10048-024-00770-y","url":null,"abstract":"Background: The ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients.Methods: We have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles.Findings: We report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74 kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy.Interpretation: This study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"393-403"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556069","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

Genotypic and phenotypic analysis of Korean patients with tuberous sclerosis complex. 韩国结节性硬化综合症患者的基因型和表型分析。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-10-01 Epub Date: 2024-08-07 DOI: 10.1007/s10048-024-00777-5

Hui Jin Shin, Sangbo Lee, Se Hee Kim, Joon Soo Lee, Ji Young Oh, Ara Ko, Hoon-Chul Kang

{"title":"Genotypic and phenotypic analysis of Korean patients with tuberous sclerosis complex.","authors":"Hui Jin Shin, Sangbo Lee, Se Hee Kim, Joon Soo Lee, Ji Young Oh, Ara Ko, Hoon-Chul Kang","doi":"10.1007/s10048-024-00777-5","DOIUrl":"10.1007/s10048-024-00777-5","url":null,"abstract":"Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder caused by mutations in the TSC1 or TSC2 gene. The aim of this study was to analyze the genotypes and phenotypes of Korean patients diagnosed with TSC and expand our understanding of this disorder. This retrospective observational study included 331 patients clinically diagnosed with TSC between November 1990 and April 2023 at Severance Children's Hospital, Seoul, South Korea. The demographic and clinical characteristics of the patients were investigated. Thirty novel variants were identified. Of the 331 patients, 188 underwent genetic testing, and genotype-phenotype variation was analyzed according to the type of gene mutation and functional domain. Fourty-nine patients (49/188, 26%) were had TSC1 mutations, 103 (55%) had TSC2 mutations, and 36 (19%) had no mutation identified (NMI). Hotspots were identified in exons 8 of TSC1 and exons 35 and 41 of TSC2. Patients with TSC2 mutations exhibited a significantly younger age at the time of seizure onset and had refractory epilepsy. Infantile epileptic spasms syndrome (IESS) was more common in the middle mutation domain of TSC2 than in the hamartin domain. Additionally, retinal hamartoma, cardiac rhabdomyoma, and renal abnormalities were significantly associated with TSC2 compared with other gene types. This study contributes to our understanding of TSC by expanding the genotypic spectrum with novel variants and providing insights into the clinical spectrum of patients with TSC in Korea.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"471-479"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899013","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

Unraveling the three-dimensional (3D) genome architecture in Neurodevelopmental Disorders (NDDs). 揭示神经发育障碍（NDDs）的三维（3D）基因组结构。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-10-01 Epub Date: 2024-08-27 DOI: 10.1007/s10048-024-00774-8

P Carballo-Pacoret, A Carracedo, C Rodriguez-Fontenla

{"title":"Unraveling the three-dimensional (3D) genome architecture in Neurodevelopmental Disorders (NDDs).","authors":"P Carballo-Pacoret, A Carracedo, C Rodriguez-Fontenla","doi":"10.1007/s10048-024-00774-8","DOIUrl":"10.1007/s10048-024-00774-8","url":null,"abstract":"The human genome, comprising millions of pairs of bases, serves as the blueprint of life, encoding instructions for cellular processes. However, genomes are not merely linear sequences; rather, the complex of DNA and histones, known as chromatin, exhibits complex organization across various levels, which profoundly influence gene expression and cellular function. Central to understanding genome organization is the emerging field of three-dimensional (3D) genome studies. Utilizing advanced techniques such as Hi-C, researchers have unveiled non-random dispositions of genomic elements, highlighting their importance in transcriptional regulation and disease mechanisms. Topologically Associating Domains (TADs), that demarcate regions of chromatin with preferential internal interactions, play crucial roles in gene regulation and are increasingly implicated in various diseases such as cancer and schizophrenia. However, their role in Neurodevelopmental Disorders (NDDs) remains poorly understood. Here, we focus on TADs and 3D conservation across the evolution and between cell types in NDDs. The investigation into genome organization and its impact on disease has led to significant breakthroughs in understanding NDDs etiology such ASD (Autism Spectrum Disorder). By elucidating the wide spectrum of ASD manifestations, researchers aim to uncover the underlying genetic and epigenetic factors contributing to its heterogeneity. Moreover, studies linking TAD disruption to NDDs underscore the importance of spatial genome organization in maintaining proper brain development and function. In summary, this review highlights the intricate interplay between genome organization, transcriptional control, and disease pathology, shedding light on fundamental biological processes and offering insights into the mechanisms underlying NDDs like ASD.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"293-305"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074643","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

Impact of flexible assertive community treatment model (FACT) on community rehabilitation of schizophrenia in Southern China. 灵活自主社区治疗模式（FACT）对华南地区精神分裂症社区康复的影响。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-10-01 Epub Date: 2024-10-21 DOI: 10.1007/s10048-024-00778-4

Yinglin Zhao, Shaoxiong Zheng, Handi Zhang, Yinnan Zhang, Zidong Wang, Qingjun Huang

{"title":"Impact of flexible assertive community treatment model (FACT) on community rehabilitation of schizophrenia in Southern China.","authors":"Yinglin Zhao, Shaoxiong Zheng, Handi Zhang, Yinnan Zhang, Zidong Wang, Qingjun Huang","doi":"10.1007/s10048-024-00778-4","DOIUrl":"10.1007/s10048-024-00778-4","url":null,"abstract":"Schizophrenia is a group of severe mental illnesses of unknown etiology, most of which are slow or subacute in young adults. 160 adult schizophrenic patients were randomly divided into an intervention group given FACT and a control group given routine mental health follow-up. The scale includes the Positive and Negative Syndrome Scale (PANSS), Social Disability Screening Schedule Scale (SDSS), and the World Health Organization's multicultural quality of life instrument in its brief form Scale(WHOQOL-BREF) were recorded. The average scores of positive scale, negative scale, general psychopathology scale and total score in PANSS scale before intervention(baseline) of the patients in the intervention group were 24.90 ± 5.43, 17.53 ± 3.84, 38.31 ± 4.09 and 80.54 ± 6.75. After 6 months and 12 months of intervention, positive scale, negative scale, general psychopathology scale and total score of the PANSS scale in the intervention group and the total score of SDSS all decreased significantly. The WHOQOL-BREF total score was significantly improved, and the differences were statistically significant (P < 0.05). The FACT intervention model has a significant effect on the rehabilitation of patients with schizophrenia in the community, improves their social function, and improves their quality of life.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"481-486"},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481849","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 novel variant in the GNE gene in a Malian patient presenting with distal myopathy. 马里一名远端肌病患者的 GNE 基因出现新变异。

IF 1.6 4区医学

Neurogenetics Pub Date : 2024-10-01 Epub Date: 2024-08-01 DOI: 10.1007/s10048-024-00761-z

Mahamadou Kotioumbé, Alassane B Maiga, Salia Bamba, Lassana Cissé, Salimata Diarra, Salimata Diallo, Abdoulaye Yalcouyé, Fousseyni Kané, Seybou H Diallo, Dramane Coulibaly, Thomas Coulibaly, Kékouta Dembélé, Boubacar Maiga, Cheick O Guinto, Guida Landouré

引用次数: 0