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
We report a case of a patient dementia with Lewy bodies carrying combinedPSEN1 andATP7B 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.Ile408ThrPSEN1 variant and a homozygous p.Arg616TrpATP7B variant. This case reinstates the need of consideringATP7B mutations when evaluating a patient with parkinsonism and supports p.Ile408Thr as a pathogenicPSEN1 variant. (Source: Neurogenetics)
Source: Neurogenetics - September 17, 2022 Category: Genetics & Stem Cells Source Type: research
Expanding the phenotypic spectrum of Dejerine-Sottas syndrome caused by the trembler mutation
This report extends the clinical spectrum of the Trembler mutation in humans to include associated hearing loss with cognitive impairment. (Source: Neurogenetics)
Source: Neurogenetics - August 16, 2022 Category: Genetics & Stem Cells Source Type: research
A Cockayne-like phenotype resulting from a de novo variant in MORC2: expanding the phenotype of MORC2-related disorders
AbstractCockayne 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 inMORC2, a gene also involved in DNA repair. Using exome sequencing, we identified a de novo pathogenic variant inMORC2 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 inMORC2 reported in the literature, we sugges...
Source: Neurogenetics - August 3, 2022 Category: Genetics & Stem Cells Source Type: research
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
AbstractProgressive 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 byNAXE 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, mol...
Source: Neurogenetics - July 11, 2022 Category: Genetics & Stem Cells Source Type: research
Reduced penetrance of an eastern French mutation in ATL1 autosomal-dominant inheritance (SPG3A): extended phenotypic spectrum coupled with brain 18F-FDG PET
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). (Source: Neurogenetics)
Source: Neurogenetics - July 5, 2022 Category: Genetics & Stem Cells Source Type: research
Genetic analysis of 18 families with tuberous sclerosis complex
AbstractTuberous sclerosis complex (TSC) is mainly caused by variants inTSC1 andTSC2, which encodes hamartin protein and tuberin protein, respectively. Here, we report clinical and molecular characteristics of 18 families with TSC. High-throughput DNA sequencing was employed to detect variants in all the exons and flanking region ofTSC1 andTSC2. TA clone and real-time PCR were performed to verify the pathogenicity of candidate variants. A total of 17 mutations were identified, including 13 mutations inTSC2 and 4 mutations inTSC1. Fifty-six percent (10/18) of the families carried de novo mutations, and 8 of these mutations ...
Source: Neurogenetics - May 21, 2022 Category: Genetics & Stem Cells Source Type: research
Molecular characterization of Turkish patients with demyelinating Charcot-Marie-Tooth disease
In this study, we investigated the molecular characteristics of a Turkish cohort of 23 probands out of 34 symptomatic demyelinating CMT individuals from January 2019 to December 2021. In order to identify the underlying genetic cause, we applied a rational algorithm:PMP22 gene was initially analyzed for duplication, ifPMP22-duplication testing was negative, other most causative genes (GJB1,MPZ) andPMP22 were then sequenced and if no variant was detected at aforementioned tests, whole exome sequencing (WES) test was finally performed. A total of 17 patients ( ≅ 74%;n = 23) were found to harbor a disease-causing vari...
Source: Neurogenetics - May 13, 2022 Category: Genetics & Stem Cells Source Type: research
