Neurogenetics最新文献_第10页

Neurodegeneration with brain iron accumulation: a case series highlighting phenotypic and genotypic diversity in 20 Indian families. 神经变性伴脑铁积累:20个印度家庭中突出表型和基因型多样性的病例系列。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-04-01 DOI: 10.1007/s10048-023-00712-0

Haseena Sait, Somya Srivastava, Manmohan Pandey, Deepak Ravichandran, Anju Shukla, Kausik Mandal, Deepti Saxena, Arya Shambhavi, Purvi Majethia, Lakshmi Priya Rao, Suvasini Sharma, Shubha R Phadke, Amita Moirangthem

{"title":"Neurodegeneration with brain iron accumulation: a case series highlighting phenotypic and genotypic diversity in 20 Indian families.","authors":"Haseena Sait, Somya Srivastava, Manmohan Pandey, Deepak Ravichandran, Anju Shukla, Kausik Mandal, Deepti Saxena, Arya Shambhavi, Purvi Majethia, Lakshmi Priya Rao, Suvasini Sharma, Shubha R Phadke, Amita Moirangthem","doi":"10.1007/s10048-023-00712-0","DOIUrl":"https://doi.org/10.1007/s10048-023-00712-0","url":null,"abstract":"Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term encompassing various inherited neurological disorders characterised by abnormal iron accumulation in basal ganglia. We aimed to study the clinical, radiological and molecular spectrum of disorders with NBIA. All molecular-proven cases of NBIA presented in the last 5 years at 2 tertiary care genetic centres were compiled. Demographic details and clinical and neuroimaging findings were collated. We describe 27 individuals from 20 unrelated Indian families with causative variants in 5 NBIA-associated genes. PLA2G6-associated neurodegeneration (PLAN) was the most common, observed in 13 individuals from 9 families. They mainly presented in infancy with neuroregression and hypotonia. A recurrent pathogenic variant in COASY was observed in two neonates with prenatal-onset severe neurodegeneration. Pathogenic bi-allelic variants in PANK2, FA2H and C19ORF12 genes were observed in the rest, and these individuals presented in late childhood and adolescence with gait abnormalities and extrapyramidal symptoms. No intrafamilial and interfamilial variability were observed. Iron deposition on neuroimaging was seen in only 6/17 (35.3%) patients. A total of 22 causative variants across 5 genes were detected including a multiexonic duplication in PLA2G6. The variants c.1799G > A and c.2370 T > G in PLA2G6 were observed in three unrelated families. In silico assessments of 8 amongst 9 novel variants were also performed. We present a comprehensive compilation of the phenotypic and genotypic spectrum of various subtypes of NBIA from the Indian subcontinent. Clinical presentation of NBIAs is varied and not restricted to extrapyramidal symptoms or iron accumulation on neuroimaging.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"113-127"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344825","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: 1

Two patients with KDM3B variants and new presentations of Diets-Jongmans syndrome. 2例KDM3B变异患者和新出现的Diets-Jongmans综合征。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-04-01 DOI: 10.1007/s10048-023-00711-1

Xiangyue Zhao, Tingting Yu, Jie Tang, Ru-En Yao, Niu Li, Jian Wang

{"title":"Two patients with KDM3B variants and new presentations of Diets-Jongmans syndrome.","authors":"Xiangyue Zhao, Tingting Yu, Jie Tang, Ru-En Yao, Niu Li, Jian Wang","doi":"10.1007/s10048-023-00711-1","DOIUrl":"https://doi.org/10.1007/s10048-023-00711-1","url":null,"abstract":"KDM3B is located on chromosome 5q31 and encodes KDM3B, which is involved in histone demethylation and epigenetic regulation. Pathogenic KDM3B variants cause a dominantly inherited disorder presenting with intellectual disability (ID), short stature, and facial dysmorphism, named Diets-Jongmans syndrome. We describe two patients with KDM3B variants presenting with Diets-Jongmans syndrome. Genetic testing was performed because of the clinical data and a lack of a clear diagnosis in both patients. Candidate variants were verified by Sanger sequencing. After KDM3B variants were detected, in silico tools were used to predict the pathogenicity of the missense variants. A minigene assay was performed to evaluate the splicing effects of the c.5070 + 1G > A variant on KDM3B. Patient 1 mainly presented with repetitive upper respiratory tract infection and patient 2 presented with palpitation, shortness of breath, and pitting edema; both had ID. Whole exome sequencing identified variants of KDM3B. Patient 1 had the de novo KDM3B c.5070 + 1G > A variant, whereas patient 2 had the c.2828G > A (p.R943Q) variant. Transcriptional experiments of the splicing variant c.5070 + 1G > A revealed aberrant transcripts leading to truncated protein products. We found two pathogenic variants in KDM3B, one of which is novel. Both patients had additional clinical presentations, and patient 1 had transient neutropenia. KDM3B c.5070 + 1G > A is the first KDM3B splice-site variant and was identified as a germline variant. Neutropenia and cardiomyopathy are newly found presentations of Diets-Jongmans syndrome. Our report enriches our knowledge of the genotypic spectrum of the KDM3B variants and phenotypic diversity of Diets-Jongmans syndrome.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"95-101"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9291057","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: 1

Clinical features of CNOT3-associated neurodevelopmental disorder in three Chinese patients. 3例中国患者cnnot3相关神经发育障碍的临床特征

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-04-01 DOI: 10.1007/s10048-023-00713-z

Peiwei Zhao, Qingjie Meng, Chunhui Wan, Tao Lei, Lei Zhang, Xiankai Zhang, Li Tan, Hongmin Zhu, Xuelian He

{"title":"Clinical features of CNOT3-associated neurodevelopmental disorder in three Chinese patients.","authors":"Peiwei Zhao, Qingjie Meng, Chunhui Wan, Tao Lei, Lei Zhang, Xiankai Zhang, Li Tan, Hongmin Zhu, Xuelian He","doi":"10.1007/s10048-023-00713-z","DOIUrl":"https://doi.org/10.1007/s10048-023-00713-z","url":null,"abstract":"CNOT3 is the central component of the CCR4-NOT protein complex, which is a global regulator of RNA polymerase II transcription. Loss of function mutations in CNOT3 lead to intellectual developmental disorder with speech delay, autism, and dysmorphic facies (IDDSADF), which is very rare. Herein, we reported two novel heterozygous frameshift mutations (c.1058_1059insT and c.724delT) and one novel splice site variant (c.387 + 2 T > C) in CNOT3 (NM_014516.3) gene in three Chinese patients with dysmorphic features, developmental delay, and behavior anomalies. The functional study showed that the CNOT3 mRNA levels were significantly decreased in the peripheral blood of two patients with c.1058_1059insT and c.387 + 2 T > C variants, respectively, and minigene assay demonstrated that the splice variant (c.387 + 2 T > C) resulted in exon skipping. We also found that CNOT3 deficiency was linked to alterations of expression levels of other CCR4-NOT complex subunits in mRNA level in the peripheral blood. By analyzing the clinical manifestations of all these patients with CNOT3 variants, including our three cases and 22 patients previously reported, we did not observe a correlation between genotypes and phenotypes. In summary, this is the first time to report cases with IDDSADF in the Chinese population, and three novel CNOT3 variants in these patients expand its mutational spectrum.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"129-136"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9292174","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 KRIT1/CCM1 mutation accompanied by a NOTCH3 mutation in a Chinese family with multiple cerebral cavernous malformations. 在中国多发性脑海绵状血管病家族中发现一种新的KRIT1/CCM1突变伴随NOTCH3突变

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-04-01 DOI: 10.1007/s10048-023-00714-y

Chunwang Li, Penghui Liu, Weilin Huang, Haojie Wang, Ke Ma, Lingyun Zhuo, Yaqing Kang, Qiu He, Yuanxiang Lin, Dezhi Kang, Fuxin Lin

{"title":"A novel KRIT1/CCM1 mutation accompanied by a NOTCH3 mutation in a Chinese family with multiple cerebral cavernous malformations.","authors":"Chunwang Li, Penghui Liu, Weilin Huang, Haojie Wang, Ke Ma, Lingyun Zhuo, Yaqing Kang, Qiu He, Yuanxiang Lin, Dezhi Kang, Fuxin Lin","doi":"10.1007/s10048-023-00714-y","DOIUrl":"https://doi.org/10.1007/s10048-023-00714-y","url":null,"abstract":"Family cerebral cavernous malformations (FCCMs) are mainly inherited through the mutation of classical CCM genes, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. FCCMs can cause severe clinical symptoms, including epileptic seizures, intracranial hemorrhage (ICH), or functional neurological deficits (FNDs). In this study, we reported a novel mutation in KRIT1 accompanied by a NOTCH3 mutation in a Chinese family. This family consists of 8 members, 4 of whom had been diagnosed with CCMs using cerebral MRI (T1WI, T2WI, SWI). The proband (II-2) and her daughter (III-4) had intracerebral hemorrhage and refractory epilepsy, respectively. Based on whole-exome sequencing (WES) data and bioinformatics analysis from 4 patients with multiple CCMs and 2 normal first-degree relatives, a novel KRIT1 mutation, NG_012964.1 (NM_194456.1): c.1255-1G > T (splice-3), in intron 13 was considered a pathogenic gene in this family. Furthermore, based on 2 severe and 2 mild CCM patients, we found an SNV missense mutation, NG_009819.1 (NM_000435.2): c.1630C > T (p.R544C), in NOTCH3. Finally, the KRIT1 and NOTCH3 mutations were validated in 8 members using Sanger sequencing. This study revealed a novel KRIT1 mutation, NG_012964.1 (NM_194456.1): c.1255-1G > T (splice-3), in a Chinese CCM family, which had not been reported previously. Moreover, the NOTCH3 mutation NG_009819.1 (NM_000435.2): c.1630C > T (p.R544C) might be a second hit and associated with the progression of CCM lesions and severe clinical symptoms.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"137-146"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9292355","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

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-04-01 DOI: 10.1007/s10048-023-00709-9

Laura Hecher, Frederike L Harms, Jasmin Lisfeld, Malik Alawi, Jonas Denecke, Kerstin Kutsche

{"title":"INPP4A-related genetic and phenotypic spectrum and functional relevance of subcellular targeting of INPP4A isoforms.","authors":"Laura Hecher, Frederike L Harms, Jasmin Lisfeld, Malik Alawi, Jonas Denecke, Kerstin Kutsche","doi":"10.1007/s10048-023-00709-9","DOIUrl":"https://doi.org/10.1007/s10048-023-00709-9","url":null,"abstract":"Type I inositol polyphosphate-4-phosphatase (INPP4A) belongs to the group of phosphoinositide phosphatases controlling proliferation, apoptosis, and endosome function by hydrolyzing phosphatidylinositol 3,4-bisphosphate. INPP4A produces multiple transcripts encoding shorter and longer INPP4A isoforms with hydrophilic or hydrophobic C-terminus. Biallelic INPP4A truncating variants cause a spectrum of neurodevelopmental disorders ranging from moderate intellectual disability to postnatal microcephaly with developmental and epileptic encephalopathy and (ponto)cerebellar hypoplasia. We report a girl with the novel homozygous INPP4A variant NM_001134224.2:c.2840del/p.(Gly947Glufs*12) (isoform d). She presented with postnatal microcephaly, global developmental delay, visual impairment, myoclonic seizures, and pontocerebellar hypoplasia and died at the age of 27 months. The level of mutant INPP4A mRNAs in proband-derived leukocytes was comparable to controls suggesting production of C-terminally altered INPP4A isoforms. We transiently expressed eGFP-tagged INPP4A isoform a (NM_004027.3) wildtype and p.(Gly908Glufs*12) mutant [p.(Gly947Glufs*12) according to NM_001134224.2] as well as INPP4A isoform b (NM_001566.2) wildtype and p.(Asp915Alafs*2) mutant, previously reported in family members with moderate intellectual disability, in HeLa cells and determined their subcellular distributions. While INPP4A isoform a was preferentially found in perinuclear clusters co-localizing with the GTPase Rab5, isoform b showed a net-like distribution, possibly localizing near and/or on microtubules. Quantification of intracellular localization patterns of the two INPP4A mutants revealed significant differences compared with the respective wildtype and similarity with each other. Our data suggests an important non-redundant function of INPP4A isoforms with hydrophobic or hydrophilic C-terminus in the brain.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"79-93"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344779","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

Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT. 扩展了一名伊朗女孩在GAMT中携带纯合子移码变异的瓜苷乙酸甲基转移酶缺乏症的神经影像学发现。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-04-01 DOI: 10.1007/s10048-022-00708-2

Seyedeh Atiyeh Afjei, Mohammad Farid Mohammadi, Elham Pourbakhtyaran, Homa Ghabeli, Mahmoud Reza Ashrafi, Roya Haghighi, Maryam Rasulinezhad, Neda Pak, Ali Reza Tavasoli, Morteza Heidari

{"title":"Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT.","authors":"Seyedeh Atiyeh Afjei, Mohammad Farid Mohammadi, Elham Pourbakhtyaran, Homa Ghabeli, Mahmoud Reza Ashrafi, Roya Haghighi, Maryam Rasulinezhad, Neda Pak, Ali Reza Tavasoli, Morteza Heidari","doi":"10.1007/s10048-022-00708-2","DOIUrl":"https://doi.org/10.1007/s10048-022-00708-2","url":null,"abstract":"Guanidinoacetate methyltransferase deficiency (GAMTD) is a treatable neurodevelopmental disorder with normal or nonspecific imaging findings. Here, we reported a 14-month-old girl with GAMTD and novel findings on brain magnetic resonance imaging (MRI).A 14-‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍month-old female patient was referred to Myelin Disorders Clinic due to onset of seizures and developmental regression following routine vaccination at 4 months of age. Brain MRI, prior to initiation of treatment, showed high signal intensity in T2-weighted imaging in bilateral thalami, globus pallidus, subthalamic nuclei, substantia nigra, dentate nuclei, central tegmental tracts in the brainstem, and posterior periventricular white matter which was masquerading for mitochondrial leukodystrophy. Basic metabolic tests were normal except for low urine creatinine; however, exome sequencing identified a homozygous frameshift deletion variant [NM_000156: c.491del; (p.Gly164AlafsTer14)] in the GAMT. Biallelic pathogenic or likely pathogenic variants cause GAMTD. We confirmed the homozygous state for this variant in the proband, as well as the heterozygote state in the parents by Sanger sequencing.MRI features in GAMTD can mimic mitochondrial leukodystrophy. Pediatric neurologists should be aware of variable MRI findings in GAMTD since they would be misleading to other diagnoses.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 2","pages":"67-78"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344773","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

Neurogenetics: Current Topics in Cellular and Developmental Neurobiology 神经遗传学:细胞和发育神经生物学的当前主题

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-07793-7

引用次数: 0

Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia. 描述ampd2相关桥小脑发育不全的表型和遗传基础。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-01-01 DOI: 10.1007/s10048-022-00706-4

Tal Gilboa, Naama Elefant, Vardiella Meiner, Nuphar Hacohen

引用次数: 1

Whole exome screening of neurodevelopmental regression disorders in a cohort of Egyptian patients. 全外显子组筛选神经发育退行性障碍在一群埃及患者。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-01-01 DOI: 10.1007/s10048-022-00703-7

Miral M Refeat, Walaa El Naggar, Mostafa M El Saied, Ayman Kilany

{"title":"Whole exome screening of neurodevelopmental regression disorders in a cohort of Egyptian patients.","authors":"Miral M Refeat, Walaa El Naggar, Mostafa M El Saied, Ayman Kilany","doi":"10.1007/s10048-022-00703-7","DOIUrl":"https://doi.org/10.1007/s10048-022-00703-7","url":null,"abstract":"Developmental regression describes a child who begins to lose his previously acquired milestones skills after he has reached a certain developmental stage and though affects his childhood development. It is associated with neurodegenerative diseases including leukodystrophy and neuronal ceroid lipofuscinosis diseases (NCLs), one of the most frequent childhood-onset neurodegenerative disorders. The current study focused on screening causative genes of developmental regression diseases comprising neurodegenerative disorders in Egyptian patients using next-generation sequencing (NGS)-based analyses as well as developing checklist to support clinicians who are not familiar with these diseases. A total of 763 Egyptian children (1 to 11 years), mainly diagnosed with developmental regression, seizures, or visual impairment, were studied using whole exome sequencing (WES). Among 763 Egyptian children, 726 cases were early clinically and molecularly diagnosed, including 482 cases that had pediatric stroke, congenital infection, and hepatic encephalopathy; meanwhile, 192 had clearly dysmorphic features, 31 showed central nervous system (CNS) malformation, 17 were diagnosed by leukodystrophy, 2 had ataxia telangiectasia, and 2 were diagnosed with tuberous sclerosis. The remained 37 out of 763 candidates were suspected with NCLs symptoms; however, 28 were confirmed to be NCLs patients, 1 was Kaya-Barakat-Masson syndrome, 1 was diagnosed as infantile neuroaxonal dystrophy, and 7 cases required further molecular diagnosis. This study provided an NGS-based approach of the genetic causes of developmental regression and neurodegenerative diseases as it comprised different variants and de novo mutations with complex phenotypes of these diseases which in turn help in early diagnoses and counseling for affected families.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"17-28"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9823068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764988","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

Influence of different spectra of NOTCH3 variants on the clinical phenotype of CADASIL - experience from Slovakia. 不同谱NOTCH3变异对CADASIL临床表型的影响——来自斯洛伐克的经验。

IF 2.2 4区医学

Neurogenetics Pub Date : 2023-01-01 DOI: 10.1007/s10048-022-00704-6

M Juhosová, J Chandoga, F Cisárik, S Dallemule, P Ďurina, D Jarásková, P Jungová, D Kantarská, M Kvasnicová, M Mistrík, A Pastoráková, R Petrovič, A Valachová, H Zelinková, J Barošová, D Böhmer, J Štofko

{"title":"Influence of different spectra of NOTCH3 variants on the clinical phenotype of CADASIL - experience from Slovakia.","authors":"M Juhosová, J Chandoga, F Cisárik, S Dallemule, P Ďurina, D Jarásková, P Jungová, D Kantarská, M Kvasnicová, M Mistrík, A Pastoráková, R Petrovič, A Valachová, H Zelinková, J Barošová, D Böhmer, J Štofko","doi":"10.1007/s10048-022-00704-6","DOIUrl":"https://doi.org/10.1007/s10048-022-00704-6","url":null,"abstract":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular disorder causing ischaemic attacks and strokes in middle-aged adults. Though the clinical spectrum includes some typical symptoms, recognition of the disease, especially at an earlier stage, is very difficult because of the highly variable manifestation and incomplete clinical picture. Characteristic brain MRI findings and the presence of pathogenic variants in the NOTCH3 gene are fundamental for CADASIL diagnosis. In this paper, we provide the first comprehensive report on CADASIL patients from Slovakia. Altogether, we identified 23 different pathogenic variants in 35 unrelated families. In our cohort of patients with clinical suspicion of CADASIL, we found a causal genetic defect and confirmed the diagnosis in 10.2% of cases. We present the case reports with up-to-date unpublished NOTCH3 variants and describe their phenotype-genotype correlation: p.(Cys65Phe), p.(Pro86Leu/Ser502Phe), p.(Arg156*), p.(Cys408Arg), p.(Tyr423Cys), p.(Asp1720His), and p.(Asp1893Thrfs*13). The most frequently described location for pathogenic variants was in exon 4, whereas the most common single variant was p.Arg1076Cys in exon 20. Based on the results of our study, we propose a re-evaluation of the criteria for the selection of patients suitable for NOTCH3 gene analysis. We hereby state that the currently used protocol of a high score requirement is not ideal for assessing molecular analysis, and it will be desirable to be less strict in criteria for genetic testing.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"24 1","pages":"1-16"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10777086","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: 1