Neurogenetics最新文献

{"title":"A novel biallelic variant further delineates PRDX3-related autosomal recessive cerebellar ataxia.","authors":"Misbahuddin M Rafeeq,&nbsp;Muhammad Umair,&nbsp;Muhammad Bilal,&nbsp;Alaa Hamed Habib,&nbsp;Ahmed Waqas,&nbsp;Ziaullah M Sain,&nbsp;Mohammad Zubair Alam,&nbsp;Raja Hussain Ali","doi":"10.1007/s10048-022-00701-9","DOIUrl":"https://doi.org/10.1007/s10048-022-00701-9","url":null,"abstract":"<p><p>Cerebellar ataxias (CAs) comprise a rare group of neurological disorders characterized by extensive phenotypic and genetic heterogeneity. In the last several years, our understanding of the CA etiology has increased significantly and resulted in the discoveries of numerous ataxia-associated genes. Herein, we describe a single affected individual from a consanguineous family segregating a recessive neurodevelopmental disorder. The proband showed features such as global developmental delay, cerebellar atrophy, hypotonia, speech issues, dystonia, and profound hearing impairment. Whole-exome sequencing and Sanger sequencing revealed a biallelic nonsense variant (c.496A > T; p.Lys166*) in the exon 5 of the PRDX3 gene that segregated perfectly within the family. This is the third report that associates the PRDX3 gene variant with cerebellar ataxia. In addition, associated hearing impairment further delineates the PRDX3 associated gene phenotypes.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"55-60"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10776581","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":"Expanding the phenotypic spectrum of Dejerine-Sottas syndrome caused by the trembler mutation.","authors":"Mustafa Jaffry,&nbsp;Soumya Bouchachi,&nbsp;Mohsen Ahmed,&nbsp;Steve N Gad,&nbsp;Swati Sathe,&nbsp;Nizar Souayah","doi":"10.1007/s10048-022-00698-1","DOIUrl":"https://doi.org/10.1007/s10048-022-00698-1","url":null,"abstract":"<p><p>Dejerine-Sottas syndrome (DSS) is the earlier onset, more severe form of Charcot-Marie-Tooth (CMT) disease with heterogenous neurologic manifestations in addition to the peripheral neuropathy depending not only on the underlying causative gene but also the specific mutation. The Trembler mutation is an uncommon missense mutation in the PMP22 gene, the most commonly mutated gene responsible for CMT. We report two cases of DSS in a mother and son with the Trembler mutation, with associated findings of hearing loss and cognitive impairment. The mother had developmental gait abnormalities and became wheelchair bound in adolescence. She displayed impairment on cognitive and audiologic testing. Her son had similar developmental gait abnormalities and became wheelchair bound at age 19. Cognitive function showed an earlier decline in the son as compared to his mother. This report extends the clinical spectrum of the Trembler mutation in humans to include associated hearing loss with cognitive impairment.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 4","pages":"275-277"},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40618661","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":"Acknowledgement to referees 2021/2022","authors":"","doi":"10.1007/s10048-022-00702-8","DOIUrl":"https://doi.org/10.1007/s10048-022-00702-8","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 1","pages":"285 - 285"},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44486322","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 Cockayne-like phenotype resulting from a de novo variant in MORC2: expanding the phenotype of MORC2-related disorders.","authors":"Amytice Mirchi,&nbsp;Alexa Derksen,&nbsp;Luan T Tran,&nbsp;Isabelle De Bie,&nbsp;Amélie Nadeau,&nbsp;Audrey Lovett,&nbsp;Anja Raams,&nbsp;Wim Vermeulen,&nbsp;Arjan F Theil,&nbsp;Geneviève Bernard","doi":"10.1007/s10048-022-00697-2","DOIUrl":"https://doi.org/10.1007/s10048-022-00697-2","url":null,"abstract":"<p><p>Cockayne syndrome is a rare inherited DNA repair multisystemic disorder. Here, we aim to raise awareness of the phenotypic resemblances between Cockayne syndrome and the neurodevelopmental disorder caused by pathogenic variants in MORC2, a gene also involved in DNA repair. Using exome sequencing, we identified a de novo pathogenic variant in MORC2 in our patient. Our patient's phenotype was characterized by multiple features evocative of Cockayne syndrome. Based on our patient's phenotype, in addition to the phenotypic description of patients with pathogenic variants in MORC2 reported in the literature, we suggest that pathogenic variants in this gene are associated with a Cockayne-like phenotype.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 4","pages":"271-274"},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40578070","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 novel homozygous mutation in NAXE gene associated with early-onset progressive encephalopathy by whole-exome sequencing: in silico protein structure characterization, molecular docking, and dynamic simulation.","authors":"Marwa Maalej,&nbsp;Lamia Sfaihi,&nbsp;Marwa Ammar,&nbsp;Fakher Frikha,&nbsp;Marwa Kharrat,&nbsp;Olfa Alila-Fersi,&nbsp;Emna Mkaouar-Rebai,&nbsp;Abdelaziz Tlili,&nbsp;Thouraya Kammoun,&nbsp;Faiza Fakhfakh","doi":"10.1007/s10048-022-00696-3","DOIUrl":"https://doi.org/10.1007/s10048-022-00696-3","url":null,"abstract":"<p><p>Progressive encephalopathy with brain edema and/or leukoencephalopathy, PEBEL1, is a severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration associated with a febrile illness. PEBEL1 is a lethal encephalopathy caused by NAXE gene mutations. Here we report a 6-month-old boy with mitochondrial encephalomyopathy from a consanguineous family. Molecular analysis was performed using whole-exome sequencing followed by segregation analysis. In addition, in silico prediction tools and molecular dynamic approaches were used to predict the structural effect of the mutation. Furthermore, molecular docking of the substrate NADP in both wild-type and mutated NAXE protein was carried out. Molecular analysis revealed the presence of the novel homozygous mutation c.641 T > A (p. Ile214Asn) in the NAXE gene, located at the NAD (P)H hydrate epimerase domain. In addition, bioinformatics analyses and molecular dynamics revealed that p. Ile214Asn mutation could affect the structure, stability, and compactness of the NAXE protein. Moreover, the result of the molecular docking showed that the p. Ile214Asn mutation leads to conformational changes in the catalytic cavity, thus modifying interaction with the substrate and restricting its access. We also compared the phenotype of our patient with those of previously reported cases with PEBEL syndrome. All bioinformatics findings provide evidence that the NAXE variant Asn214 disrupts NAXE protein functionality leading to an insufficient NAD (P)HX repair system and the development of clinical features of PEBEL1 syndrome in our patient. To our knowledge, our case is the 21st case of PEBEL1 patient worldwide and the first case in North Africa.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 4","pages":"257-270"},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40585333","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":"CTBP1 and CTBP2 mutations underpinning neurological disorders: a systematic review.","authors":"Natalia Acosta-Baena,&nbsp;Johanna Alexandra Tejada-Moreno,&nbsp;Mauricio Arcos-Burgos,&nbsp;Carlos Andrés Villegas-Lanau","doi":"10.1007/s10048-022-00700-w","DOIUrl":"https://doi.org/10.1007/s10048-022-00700-w","url":null,"abstract":"<p><p>C-terminal binding proteins (CtBP1/2) are transcriptional coregulators that play a significant role during vertebrate neurodevelopment. This systematic review aims to identify case reports with genetic variants in CTBP1 and CTBP2 associated with brain development syndromes.We screened different databases (PubMed, Scopus, Google Scholar, LILACS) by systematically searching journals and checking reference lists and citations of background papers. We found fourteen cases (10 males) from five papers carrying two pathogenic, heterozygous variants in the CTBP1 gene (13 individuals carried the missense mutation c.991C T, p.Arg342Trp, and one subject carrying the 2-base pair deletion c.1315_1316delCA, p.Gln439ValfsTer84). These mutations were de novo in 13 cases and one case of maternal germinal mosaicism. Two variants are in the same domain of the protein: Pro-Leu-Asp-Leu-Ser (PLDLS) C terminal. Patients with these mutations exhibit a phenotype with intellectual disability, HADDTS syndrome (hypotonia, ataxia, developmental delay, and tooth enamel defects), and cerebellar volume loss. We did not identify reported cases associated with homozygous mutations harbored in CTBP1. We did not identify any report of neurodevelopment phenotypes associated with heterozygous or homozygous CTBP2 mutations. Due to CTBP2/RIBEYE being a gene with dual function, identifying and interpreting the potential pathogenic variants is challenging.Further, homozygous mutations in the CTBP2 gene may be lethal. The mechanisms involved in the pathogenesis of neurodevelopment due to variants of these proteins have not yet been elucidated, despite some functional evidence. Further studies should be conducted to understand these transcription factors and their interaction with each other and their partners.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 4","pages":"231-240"},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40454299","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}

{"title":"Whole-exome sequencing reveals PSEN1 and ATP7B combined variants as a possible cause of early-onset Lewy body dementia: a case study of genotype-phenotype correlation.","authors":"Miguel Tábuas-Pereira,&nbsp;Rita Guerreiro,&nbsp;Célia Kun-Rodrigues,&nbsp;Maria Rosário Almeida,&nbsp;José Brás,&nbsp;Isabel Santana","doi":"10.1007/s10048-022-00699-0","DOIUrl":"10.1007/s10048-022-00699-0","url":null,"abstract":"<p><p>Dementia with Lewy bodies is a neurodegenerative disease, sharing features with Parkinson's and Alzheimer's diseases. We report a case of a patient dementia with Lewy bodies carrying combined PSEN1 and ATP7B mutations. A man developed dementia with Lewy bodies starting at the age of 60 years. CSF biomarkers were of Alzheimer's disease and DaTSCAN was abnormal. Whole-exome sequencing revealed a heterozygous p.Ile408Thr PSEN1 variant and a homozygous p.Arg616Trp ATP7B variant. This case reinstates the need of considering ATP7B mutations when evaluating a patient with parkinsonism and supports p.Ile408Thr as a pathogenic PSEN1 variant.</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 4","pages":"279-283"},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669161/pdf/nihms-1838143.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40365178","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}

{"title":"Reduced penetrance of an eastern French mutation in ATL1 autosomal-dominant inheritance (SPG3A): extended phenotypic spectrum coupled with brain ¹⁸F-FDG PET.","authors":"Armand Hocquel,&nbsp;Jean-Marie Ravel,&nbsp;Laetitia Lambert,&nbsp;Céline Bonnet,&nbsp;Guillaume Banneau,&nbsp;Bophara Kol,&nbsp;Laurène Tissier,&nbsp;Lucie Hopes,&nbsp;Mylène Meyer,&nbsp;Céline Dillier,&nbsp;Maud Michaud,&nbsp;Arnaud Lardin,&nbsp;Anne-Laure Kaminsky,&nbsp;Emmanuelle Schmitt,&nbsp;Liang Liao,&nbsp;François Zhu,&nbsp;Bronner Myriam,&nbsp;Carine Bossenmeyer-Pourié,&nbsp;Antoine Verger,&nbsp;Mathilde Renaud","doi":"10.1007/s10048-022-00695-4","DOIUrl":"https://doi.org/10.1007/s10048-022-00695-4","url":null,"abstract":"<p><p>ATL1-related spastic paraplegia SPG3A is a pure form of hereditary spastic paraplegia. Rare complex phenotypes have been described, but few data concerning cognitive evaluation or molecular imaging of these patients are available. We relate a retrospective collection of patients with SPG3A from the Neurology Department of Nancy University Hospital, France. For each patient were carried out a ¹⁸F-FDG PET (positron emission tomography), a electromyography (EMG), a sudoscan®, a cerebral and spinal cord MRI (magnetic resonance imaging) with measurement of cervical and thoracic surfaces, a neuropsychological assessment. The present report outlines standardised clinical and paraclinical data of five patients from two east-France families carrying the same missense pathogenic variation, NM_015915.4(ATL1): c.1483C > T p.(Arg495Trp) in ATL1. Mean age at onset was 14 ± 15.01 years. Semi-quantitatively and in comparison to healthy age-matched subjects, PET scans showed a significant cerebellar and upper or mild temporal hypometabolism in all four adult patients and hypometabolism of the prefrontal cortex or precuneus in three of them. Sudoscan® showed signs of small fibre neuropathy in three patients. Cervical and thoracic patients' spinal cords were significantly thinner than matched-control, respectively 71 ± 6.59mm² (p = 0.01) and 35.64 ± 4.35mm² (p = 0.015). Two patients presented with a dysexecutive syndrome. While adding new clinical and paraclinical signs associated with ATL1 pathogenic variations, we insist here on the variable penetrance and expressivity. We report small fibre neuropathy, cerebellar hypometabolism and dysexecutive syndromes associated with SPG3A. These cognitive impairments and PET findings may be related to a cortico-cerebellar bundle axonopathy described in the cerebellar cognitive affective syndrome (CCAS).</p>","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 4","pages":"241-255"},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40584262","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":"Genetic analysis of 18 families with tuberous sclerosis complex","authors":"Kaili Yin, N. Lin, Q. Lu, Li-Ri Jin, Yan Huang, Xiaoping Zhou, Kaifeng Xu, Qing Liu, Xue Zhang","doi":"10.1007/s10048-022-00694-5","DOIUrl":"https://doi.org/10.1007/s10048-022-00694-5","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 1","pages":"223 - 230"},"PeriodicalIF":2.2,"publicationDate":"2022-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44092159","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":"Molecular characterization of Turkish patients with demyelinating Charcot-Marie-Tooth disease","authors":"Taner Karakaya, Ayberk Turkyilmaz, G. Sager, R. İnan, O. Yaralı, A. Çebi, Y. Akın","doi":"10.1007/s10048-022-00693-6","DOIUrl":"https://doi.org/10.1007/s10048-022-00693-6","url":null,"abstract":"","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"23 1","pages":"213 - 221"},"PeriodicalIF":2.2,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43151081","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}