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Acute demyelinating inflammatory polyneuropathy (AIDP) is the most common type of Guillain-Barré syndrome (GBS) in Europe, following several viral and bacterial infections. Data on AIDP-patients associated with SARS-CoV-2 (coronavirus-2) infection are scarce. We describe the case of a 54-years-old Caucasian female patient with typical clinical and electrophysiological manifestations of AIDP, who was reported positive with PCR for SARS-CoV-2, 3 weeks prior to onset of the neurological symptoms. She did not experience a preceding fever or respiratory symptoms, but a transient loss of smell and taste. At the admission to our neurological department, a progressive proximally pronounced paraparesis, areflexia, and sensory loss with tingling of all extremities were found, which began 10 days before. The modified Erasmus Giullain-Barré Syndrome outcome score (mEGOS) was 3/9 at admission and 1/12 at day 7 of hospitalization. The electrophysiological assessment proved a segmental demyelinating polyneuropathy and cerebrospinal fluid examination showed an albuminocytologic dissociation. The neurological symptoms improved significantly during treatment with immunoglobulins. Our case draws attention to the occurrence of GBS also in patients with COVID-19 (coronavirus disease 2019), who did not experience respiratory or general symptoms. It emphasizes that SARS-CoV-2 induces immunological processes, regardless from the lack of prodromic symptoms. However, it is likely that there is a connection between the severity of the respiratory syndrome and further neurological consequences., (© 2020 Peripheral Nerve Society.)

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, and muscle rigidity. To date, approximately 50 genes have been implicated in PD pathogenesis, including both Mendelian genes with rare mutations and low-penetrance genes with common polymorphisms. Previous studies of low-penetrance genes focused on protein-coding genes, and less attention was given to long noncoding RNAs (lncRNAs). In this study, we aimed to investigate the susceptibility roles of lncRNA gene polymorphisms in the development of PD. Therefore, polymorphisms ( n =15) of the PINK1-AS , UCHL1-AS , BCYRN1 , SOX2-OT , ANRIL and HAR1A lncRNAs genes were genotyped in Hungarian PD patients ( n =160) and age- and sex-matched controls ( n =167). The rare allele of the rs13388259 intergenic polymorphism, located downstream of the BCYRN1 gene, was significantly more frequent among PD patients than control individuals (OR = 2.31; p =0.0015). In silico prediction suggested that this polymorphism is located in a noncoding region close to the binding site of the transcription factor HNF4A, which is a central regulatory hub gene that has been shown to be upregulated in the peripheral blood of PD patients. The rs13388259 polymorphism may interfere with the binding affinity of transcription factor HNF4A, potentially resulting in abnormal expression of target genes, such as BCYRN1 .

Pathogenic variants of the gap junction beta 1 (GJB1) gene are responsible for the Charcot-Marie-Tooth neuropathy X type 1 (CMTX1). In this study, we report the mutation frequency of GJB1 in 210 Hungarian CMT patients and the phenotype comparison between male and female CMTX1 patients. Altogether, 13 missense substitutions were found in the GJB1 gene. Among them, 10 have been previously described as pathogenic variants (p.Arg15Trp, p.Val63Ile, p.Leu89Val, p.Ala96Gly, p.Arg107Trp, p.Arg142Gln, p.Arg164Trp, p.Arg164Gln, p.Pro172Ala and p.Asn205Ser), while 3 were novel, likely pathogenic alterations (p.Val13Glu, p.Glu186Gly, p.Met194Ile). These variants were not present in controls and were predicted as disease causing by in silico analysis. The frequency of the variants was 6.7% in our cohort which refers to a common cause of hereditary neuropathy among Hungarian patients. In addition to the classical phenotype, CNS involvement was proved in 26.1% of the CMTX1 patients. GJB1 pathogenic alterations were found mainly in males but we also detected them in female probands. The statistical analysis of CMTX1 patients revealed a significant difference between the two genders regarding the age of onset, Charcot-Marie-Tooth neuropathy and examination scores., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Many individuals with Parkinson's disease (PD) develop cognitive deficits, and a phenotypic and molecular overlap between neurodegenerative diseases exists. We investigated the contribution of rare variants in seven genes of known relevance to dementias (β-amyloid precursor protein (APP), PSEN1/2, MAPT (microtubule-associated protein tau), fused in sarcoma (FUS), granulin (GRN) and TAR DNA-binding protein 43 (TDP-43)) to PD and PD plus dementia (PD+D) in a discovery sample of 376 individuals with PD and followed by the genotyping of 25 out of the 27 identified variants with a minor allele frequency <5% in 975 individuals with PD, 93 cases with Lewy body disease on neuropathological examination, 613 individuals with Alzheimer's disease (AD), 182 cases with frontotemporal dementia and 1014 general population controls. Variants identified in APP were functionally followed up by Aβ mass spectrometry in transiently transfected HEK293 cells. PD+D cases harbored more rare variants across all the seven genes than PD individuals without dementia, and rare variants in APP were more common in PD cases overall than in either the AD cases or controls. When additional controls from publically available databases were added, one rare variant in APP (c.1795G>A(p.(E599K))) was significantly associated with the PD phenotype but was not found in either the PD cases or controls of an independent replication sample. One of the identified rare variants (c.2125G>A (p.(G709S))) shifted the Aβ spectrum from Aβ40 to Aβ39 and Aβ37. Although the precise mechanism remains to be elucidated, our data suggest a possible role for APP in modifying the PD phenotype as well as a general contribution of genetic factors to the development of dementia in individuals with PD.

Dynamin2 (DNM2) gene mutations may result in Charcot-Marie-Tooth disease and centronuclear myopathy. Here, we present a patient suffering from cardiomyopathy and centronuclear myopathy with repetitive discharges and mild axonal neuropathy due to DNM2 mutation. Detailed cardiological and neurological examinations, electrophysiological tests, muscle biopsy, and molecular genetic analysis were performed. The patient developed left bundle branch block at age 40 and was fitted with a pacemaker at the age of 43. The patient has severe heart failure, ptosis, strabism, facial and proximal muscle weakness. Electrophysiological investigations found myopathy, complex repetitive discharges, and axonal neuropathy. Skeletal muscle biopsy detected centronuclear myopathy and cytochrome C oxidase (COX) negative fibers. Genetic analysis detected a pathogenic c.1105C>T (p.R369W) DNM2 gene mutation and heteroplasmic multiple mitochondrial DNA (mtDNA) deletion. Our data broadens the phenotypic spectrum of DNM2 mutations. The presence of the multiple mtDNA deletions may provide new aspects to understanding the pathogenesis of multisystemic symptoms in patients with DNM2 mutations.