Neurogenetics最新文献_第6页

Dem-Aging: autophagy-related pathologies and the "two faces of dementia". Dem-Aging：自噬相关病理和 "痴呆症的两面性"。

IF 2.2 4区医学

Neurogenetics Pub Date : 2024-01-01 Epub Date: 2023-12-20 DOI: 10.1007/s10048-023-00739-3

N Gammaldi, S Doccini, S Bernardi, M Marchese, M Cecchini, R Ceravolo, S Rapposelli, G M Ratto, S Rocchiccioli, F Pezzini, F M Santorelli

{"title":"Dem-Aging: autophagy-related pathologies and the \"two faces of dementia\".","authors":"N Gammaldi, S Doccini, S Bernardi, M Marchese, M Cecchini, R Ceravolo, S Rapposelli, G M Ratto, S Rocchiccioli, F Pezzini, F M Santorelli","doi":"10.1007/s10048-023-00739-3","DOIUrl":"10.1007/s10048-023-00739-3","url":null,"abstract":"Neuronal ceroid lipofuscinosis (NCL) is an umbrella term referring to the most frequent childhood-onset neurodegenerative diseases, which are also the main cause of childhood dementia. Although the molecular mechanisms underlying the NCLs remain elusive, evidence is increasingly pointing to shared disease pathways and common clinical features across the disease forms. The characterization of pathological mechanisms, disease modifiers, and biomarkers might facilitate the development of treatment strategies.The DEM-AGING project aims to define molecular signatures in NCL and expedite biomarker discovery with a view to identifying novel targets for monitoring disease status and progression and accelerating clinical trial readiness in this field. In this study, we fused multiomic assessments in established NCL models with similar data on the more common late-onset neurodegenerative conditions in order to test the hypothesis of shared molecular fingerprints critical to the underlying pathological mechanisms. Our aim, ultimately, is to combine data analysis, cell models, and omic strategies in an effort to trace new routes to therapies that might readily be applied in the most common forms of dementia.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"39-46"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812648","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

Two novel cases of biallelic SMPD4 variants with brain structural abnormalities. 两例脑结构异常的双等位基因SMPD4变体的新病例。

IF 2.2 4区医学

Neurogenetics Pub Date : 2024-01-01 Epub Date: 2023-10-26 DOI: 10.1007/s10048-023-00737-5

Shintaro Aoki, Kazuki Watanabe, Mitsuhiro Kato, Yukihiko Konishi, Kazuo Kubota, Emiko Kobayashi, Mitsuko Nakashima, Hirotomo Saitsu

{"title":"Two novel cases of biallelic SMPD4 variants with brain structural abnormalities.","authors":"Shintaro Aoki, Kazuki Watanabe, Mitsuhiro Kato, Yukihiko Konishi, Kazuo Kubota, Emiko Kobayashi, Mitsuko Nakashima, Hirotomo Saitsu","doi":"10.1007/s10048-023-00737-5","DOIUrl":"10.1007/s10048-023-00737-5","url":null,"abstract":"Sphingomyelin phosphodiesterase 4 (SMPD4) encodes a member of the Mg2+-dependent, neutral sphingomyelinase family that catalyzes the hydrolysis of the phosphodiester bond of sphingomyelin to form phosphorylcholine and ceramide. Recent studies have revealed that biallelic loss-of-function variants of SMPD4 cause syndromic neurodevelopmental disorders characterized by microcephaly, congenital arthrogryposis, and structural brain anomalies. In this study, three novel loss-of-function SMPD4 variants were identified using exome sequencing (ES) in two independent patients with developmental delays, microcephaly, seizures, and brain structural abnormalities. Patient 1 had a homozygous c.740_741del, p.(Val247Glufs*21) variant and showed profound intellectual disability, hepatomegaly, a simplified gyral pattern, and a thin corpus callosum without congenital dysmorphic features. Patient 2 had a compound heterozygous nonsense c.2124_2125del, p.(Phe709*) variant and splice site c.1188+2dup variant. RNA analysis revealed that the c.1188+2dup variant caused exon 13 skipping, leading to a frameshift (p.Ala406Ser*6). In vitro transcription analysis using minigene system suggested that mRNA transcribed from mutant allele may be degraded by nonsense-mediated mRNA decay system. He exhibited diverse manifestations, including growth defects, muscle hypotonia, respiratory distress, arthrogryposis, insulin-dependent diabetes mellitus, sensorineural hearing loss, facial dysmorphism, and various brain abnormalities, including cerebral atrophy, hypomyelination, and cerebellar hypoplasia. Here, we review previous literatures and discuss the phenotypic diversity of SMPD4-related disorders.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"3-11"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50163891","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

Retraction Note: Clinical characterization of familial 1p36.3 microduplication. 回缩说明：家族性1p36.3微重复的临床特征。

IF 2.2 4区医学

Neurogenetics Pub Date : 2024-01-01 DOI: 10.1007/s10048-023-00735-7

Junping Jiao, Yuping Wang, Yue Hou, Chao Gao, Huimin Shi, Shujuan Tian

引用次数: 0

Correction to: New Editors-in-Chief and future directions: a glimpse into the evolving future of Neurogenetics. 更正为：新主编和未来方向：一窥神经遗传学不断发展的未来。

IF 2.2 4区医学

Neurogenetics Pub Date : 2024-01-01 DOI: 10.1007/s10048-024-00747-x

Geraldine Zimmer-Bensch

引用次数: 0

New Editors-in-Chief and future directions: a glimpse into the evolving future of Neurogenetics. 新主编和未来方向：一窥神经遗传学不断发展的未来。

IF 2.2 4区医学

Neurogenetics Pub Date : 2024-01-01 DOI: 10.1007/s10048-023-00740-w

Geraldine Zimmer-Bensch

引用次数: 0

Dem-Aging: autophagy-related pathologies and the “two faces of dementia” 衰老：自噬相关病症与 "痴呆症的两面性"

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-12-20 DOI: 10.1007/s10048-023-00739-3

N. Gammaldi, S. Doccini, S. Bernardi, M. Marchese, M. Cecchini, R. Ceravolo, S. Rapposelli, GM. Ratto, S. Rocchiccioli, F. Pezzini, F. M. Santorelli

{"title":"Dem-Aging: autophagy-related pathologies and the “two faces of dementia”","authors":"N. Gammaldi, S. Doccini, S. Bernardi, M. Marchese, M. Cecchini, R. Ceravolo, S. Rapposelli, GM. Ratto, S. Rocchiccioli, F. Pezzini, F. M. Santorelli","doi":"10.1007/s10048-023-00739-3","DOIUrl":"https://doi.org/10.1007/s10048-023-00739-3","url":null,"abstract":"Neuronal ceroid lipofuscinosis (NCL) is an umbrella term referring to the most frequent childhood-onset neurodegenerative diseases, which are also the main cause of childhood dementia. Although the molecular mechanisms underlying the NCLs remain elusive, evidence is increasingly pointing to shared disease pathways and common clinical features across the disease forms. The characterization of pathological mechanisms, disease modifiers, and biomarkers might facilitate the development of treatment strategies.The DEM-AGING project aims to define molecular signatures in NCL and expedite biomarker discovery with a view to identifying novel targets for monitoring disease status and progression and accelerating clinical trial readiness in this field. In this study, we fused multiomic assessments in established NCL models with similar data on the more common late-onset neurodegenerative conditions in order to test the hypothesis of shared molecular fingerprints critical to the underlying pathological mechanisms. Our aim, ultimately, is to combine data analysis, cell models, and omic strategies in an effort to trace new routes to therapies that might readily be applied in the most common forms of dementia.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"67 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818851","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

Atypical retinopathy in ataxia with vitamin E deficiency: report of a sibship 共济失调伴维生素 E 缺乏的非典型视网膜病变：一个兄弟姐妹的报告

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-12-18 DOI: 10.1007/s10048-023-00741-9

Stéphane Abramowicz, Alexandre Dentel, Maxime Chouraqui, Bahram Bodaghi, Sara Touhami

引用次数: 0

Family and literature analysis demonstrates phenotypic effect of two variants in the calpain-3 gene. 家族和文献分析表明钙蛋白酶-3基因中两种变体的表型效应。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-10-01 Epub Date: 2023-08-17 DOI: 10.1007/s10048-023-00728-6

Maike Tomforde, Meike Steinbach, Tobias B Haack, Gregor Kuhlenbäumer

引用次数: 0

A novel heterozygous ZBTB18 missense mutation in a family with non-syndromic intellectual disability. 一个非综合征性智力残疾家族中一个新的杂合子ZBTB18错义突变。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-10-01 Epub Date: 2023-07-31 DOI: 10.1007/s10048-023-00727-7

Nana Li, Hong Kang, Yanna Zou, Zhen Liu, Ying Deng, Meixian Wang, Lu Li, Hong Qin, Xiaoqiong Qiu, Yanping Wang, Jun Zhu, Mark Agostino, Julian I-T Heng, Ping Yu

{"title":"A novel heterozygous ZBTB18 missense mutation in a family with non-syndromic intellectual disability.","authors":"Nana Li, Hong Kang, Yanna Zou, Zhen Liu, Ying Deng, Meixian Wang, Lu Li, Hong Qin, Xiaoqiong Qiu, Yanping Wang, Jun Zhu, Mark Agostino, Julian I-T Heng, Ping Yu","doi":"10.1007/s10048-023-00727-7","DOIUrl":"10.1007/s10048-023-00727-7","url":null,"abstract":"Intellectual disability (ID) is a common neurodevelopmental disorder characterized by significantly impaired adaptive behavior and cognitive capacity. High throughput sequencing approaches have revealed the genetic etiologies for 25-50% of ID patients, while inherited genetic mutations were detected in <5% cases. Here, we investigated the genetic cause for non-syndromic ID in a Han Chinese family. Whole genome sequencing was performed on identical twin sisters diagnosed with ID, their respective children, and their asymptomatic parents. Data was filtered for rare variants, and in silico prediction tools were used to establish pathogenic alleles. Candidate mutations were validated by Sanger sequencing. In silico modeling was used to evaluate the mutation's effects on the protein encoded by a candidate coding gene. A novel heterozygous variant in the ZBTB18 gene c.1323C>G (p.His441Gln) was identified. This variant co-segregated with affected individuals in an autosomal dominant pattern and was not detected in asymptomatic family members. Molecular studies reveal that a p.His441Gln substitution disrupts zinc binding within the second zinc finger and disrupts the capacity for ZBTB18 to bind DNA. This is the first report of an inherited ZBTB18 mutation for ID. This study further validates WGS for the accurate molecular diagnosis of ID.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"251-262"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268432","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

Clinical and functional study of two de novo variations of CDKL5 gene. CDKL5基因两个新变异的临床和功能研究。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-10-01 Epub Date: 2023-08-16 DOI: 10.1007/s10048-023-00731-x

Yang You, Xinyi Men, Wenjuan Wu, Shan Liu, Xuexin He, Suzhen Sun, Xiuxia Wang, Baoguang Li

{"title":"Clinical and functional study of two de novo variations of CDKL5 gene.","authors":"Yang You, Xinyi Men, Wenjuan Wu, Shan Liu, Xuexin He, Suzhen Sun, Xiuxia Wang, Baoguang Li","doi":"10.1007/s10048-023-00731-x","DOIUrl":"10.1007/s10048-023-00731-x","url":null,"abstract":"The cyclin-dependent kinase like 5 (CDKL5) gene variation is X-linked dominant and is associated with type 2 developmental and epileptic encephalopathy (DEE). Although numerous cases of CDKL5 have been reported, there is limited discussion regarding functional verification. We described two children with DEE caused by de novo variations of CDKL5 gene, analyzed their clinical manifestations, and performed genetic testing on their gene variation sites. The two cases presented with tonic seizures followed by epileptic spasms, indicative of refractory epilepsy. Physical examination revealed abnormal facial features, including wide eye distance, low nose base, and high nose bridge. Both cases exhibited developmental disabilities. Cranial magnetic resonance imaging (MRI) showed widening of the bilateral frontotemporal extracerebral space. Genetic testing identified variations at the gene sites c.463 + 4A > G (splicing) and c.1854_1861delCAAAGTGA (p.D618Efs*18). Minigene experiments further confirmed that the intronic variation c.463 + 4A > G (splicing) disrupted splicing, leading to protein truncation. CDKL5 gene variation can lead to DEE, and intron variation site c.463 + 4A > G (splicing) can cause protein truncation, which is a pathogenic variation.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":" ","pages":"263-271"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004553","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