Reply to letter to the editor by De Michele et al
(Source: Neurogenetics)
Source: Neurogenetics - February 5, 2020 Category: Genetics & Stem Cells Source Type: research
Of cognition and cerebellum in SCA48
(Source: Neurogenetics)
Source: Neurogenetics - February 2, 2020 Category: Genetics & Stem Cells Source Type: research
POLR3A variants with striatal involvement and extrapyramidal movement disorder
AbstractBiallelic variants inPOLR3A cause 4H leukodystrophy, characterized by hypomyelination in combination with cerebellar and pyramidal signs and variable non-neurological manifestations. Basal ganglia are spared in 4H leukodystrophy, and dystonia is not prominent. Three patients with variants inPOLR3A, an atypical presentation with dystonia, and MR involvement of putamen and caudate nucleus (striatum) and red nucleus have previously been reported. Genetic, clinical findings and 18 MRI scans from nine patients with homozygous or compound heterozygousPOLR3A variants and predominant striatal changes were retrospectively r...
Source: Neurogenetics - January 14, 2020 Category: Genetics & Stem Cells Source Type: research
Changes in global gene expression indicate disordered autophagy, apoptosis and inflammatory processes and downregulation of cytoskeletal signalling and neuronal development in patients with Niemann –Pick C disease
AbstractChanges in gene expression profiles were investigated in 23 patients with Niemann –Pick C1 disease (NPC). cDNA expression microarrays with subsequent validation by qRT-PCR were used. Comparison of NPC to control samples revealed upregulation of genes involved in inflammation (MMP3,THBS4), cytokine signalling (MMP3), extracellular matrix degradation (MMP3,CTSK), autophagy and apoptosis (CTSK,GPNMB,PTGIS), immune response (AKR1C3,RCAN2,PTGIS) and processes of neuronal development (RCAN2). Downregulated genes were associated with cytoskeletal signalling (ACTG2,CNN1); inflammation and oxidative stress (CNN1); inhibit...
Source: Neurogenetics - January 10, 2020 Category: Genetics & Stem Cells Source Type: research
Identification and characterization of novel mutations in MOGS in a Chinese patient with infantile spams
In conclusion, our study suggested whole exome sequencing, and genes associated with CDGs should be analyzed in patients with infantile spams and multiple system involvement, and mutant MOGS–impaired cell cycle progression. Our work broadens the mutation spectrum ofMOGS gene. (Source: Neurogenetics)
Source: Neurogenetics - January 9, 2020 Category: Genetics & Stem Cells Source Type: research
Mitochondrial epilepsy: a cross-sectional nationwide Italian survey
AbstractMany aspects of epilepsy in mitochondrial disorders (MDs) need to be further clarified. To this aim, we explored retrospectively a cohort of individuals with MDs querying the “Nationwide Italian Collaborative Network of Mitochondrial Diseases” (NICNMD) database (1467 patients included since 2010 to December 2016). We collected information on age at epilepsy onset, seizure type and frequency, genetic findings, and antiepileptic drugs (AEDs). At the time of our survey, 147/1467 (10%) patients in the NICNMD database had epilepsy. Complete information was available only for 98 patients, 52 males and 46 females, age...
Source: Neurogenetics - January 2, 2020 Category: Genetics & Stem Cells Source Type: research
Customized multigene panels in epilepsy: the best things come in small packages
AbstractOver the past 10 years, the increasingly important role played by next-generation sequencing panels in the genetic diagnosis of epilepsy has led to a growing list of gene variants and a plethora of new scientific data. To date, however, there is still no consensus on what constitutes the “ideal panel design,” or on the most rational criteria for selecting the best candidates for gene-panel analysis, even though both might optimize the cost-benefit ratio and the diagnostic efficiency of customized gene panels. Even though more and more laboratories are adopting whole-exome sequencing as a first-tier diagn osti...
Source: Neurogenetics - December 12, 2019 Category: Genetics & Stem Cells Source Type: research
Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2
In conclusion, our work supports that the molecular diagnostic rate of CMT2 patients can be increased via whole exome sequencing, and our data suggest that assessment of possibleHINT1 mutations should be undertaken for CMT2 patients with neuromyotonia. (Source: Neurogenetics)
Source: Neurogenetics - December 11, 2019 Category: Genetics & Stem Cells Source Type: research
Neurodevelopmental phenotype associated with CHD8-SUPT16H duplication
AbstractMicrodeletions encompassing 14q11.2locus, involvingSUPT16H andCHD8, were shown to cause developmental delay, intellectual disability, autism spectrum disorders and macrocephaly. Variations leading toCHD8 haploinsufficiency or loss of function were also shown to lead to a similar phenotype. Recently, a 14q11.2 microduplication syndrome, encompassingCHD8 andSUPT16H, has been described, highlighting the importance of a tight control of at leastCHD8 gene-dosage for a normal development. There have been only a few reports of 14q11.2 microduplications. Patients showed variable neurodevelopmental issues of variable severi...
Source: Neurogenetics - December 9, 2019 Category: Genetics & Stem Cells Source Type: research
Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family
AbstractSCA48 is a novel spinocerebellar ataxia (SCA) originally and recently characterized by prominent cerebellar cognitive-affective syndrome (CCAS) and late-onset ataxia caused by mutations on theSTUB1 gene. Here, we report the first SCA48 case from Turkey with novel clinical features and diffusion tensor imaging (DTI) findings, used for the first time to evaluate a SCA48 patient. A 65-year-old female patient with slowly progressive cerebellar ataxia, cognitive impairment, behavioral changes, and a vertical family history was evaluated. Following the exclusion of repeat expansion ataxias, whole exome sequencing (WES) w...
Source: Neurogenetics - November 18, 2019 Category: Genetics & Stem Cells Source Type: research
Childhood-onset autosomal recessive ataxias: a cross-sectional study from Turkey
This study is aimed at establishing molecular classification and phenotypic correlation of childhood-onset ARAs in Southeast Anatolia of Turkey. Sixty-five children (aged 0 to 18) from 40 unrelated families who were analyzed through hereditary ataxia NGS panel between the years of 2015 –2018 were selected for the study. Seventeen different, clinically significant ARA-related pathogenic variants were detected in 33 of 40 families (82.5%), 12 of which were noted to be unreported variants. Among these 33 families, 24 hadATM-related (72.72%), four hadSACS-related (12.12%), three hadCOQ8A-related (9.09%), and two hadAPTX-rela...
Source: Neurogenetics - November 18, 2019 Category: Genetics & Stem Cells Source Type: research
A novel cysteine-sparing G73A mutation of NOTCH3 in a Chinese CADASIL family
AbstractCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disease leading to stroke and vascular dementia. CADASIL is an inherited small blood vessel disease caused by mutations in the gene encoding the neurogenic locus notch homolog protein 3 (NOTCH3). NOTCH3 is large type I membrane receptor mainly expressed in vascular smooth muscle cells and pericytes. Most identified mutations result in insert or deletion of a cysteine residue within the EGF-like repeats. To date, some cases with a cysteine-sparing mutant have been described. Genetic analy...
Source: Neurogenetics - November 12, 2019 Category: Genetics & Stem Cells Source Type: research
The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype
AbstractCharcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy with a prevalence of 1 in 2500 individuals worldwide. Here, we report three Turkish siblings from consanguineous parents presenting with a CMT-like phenotype who carry a homozygous c.493C>T, p.Arg165Cys mutation in the FXN gene that is the only known causative gene for Friedreich ’s ataxia (FRDA). The identified missense mutation has been reported previously in two FRDA cases in compound heterozygosity with the common GAA repeat expansion in the first intron of the FXN gene. Analysis of skin biopsy samples from our family indicated that ...
Source: Neurogenetics - October 30, 2019 Category: Genetics & Stem Cells Source Type: research
Giant axonal neuropathy: a multicenter retrospective study with genotypic spectrum expansion
AbstractGiant axonal neuropathy (GAN) is an autosomal recessive disease caused by mutations in theGAN gene encoding gigaxonin. Patients develop a progressive sensorimotor neuropathy affecting peripheral nervous system (PNS) and central nervous system (CNS). Methods: In this multicenter observational retrospective study, we recorded French patients withGAN mutations, and 10 patients were identified. Mean age of patients was 9.7 years (2 –18), eight patients were female (80%), and all patients met infant developmental milestones and had a family history of consanguinity. Mean age at disease onset was 3.3 years (1–5), and...
Source: Neurogenetics - October 25, 2019 Category: Genetics & Stem Cells Source Type: research
Infectious stress triggers a POLG-related mitochondrial disease
This study underscores the benefit of early genetic diagnosis of the patients with mitochondrial diseases, since they may be a target group of patients especially vulnerable to environmental factors. (Source: Neurogenetics)
Source: Neurogenetics - October 25, 2019 Category: Genetics & Stem Cells Source Type: research
