Cerebellar Ataxia as a Common Clinical Presentation Associated with DNMT1 p.Y511H and a Review of the Literature

In this study, we report on the cases of a kindred carrying theDNMT1 variant NM_001130823.2:c.1531 T  >  C (p.Y511H) presenting with the ADCA-DN phenotype. The review of the literature further revealed that later ages at onset and the presence of cerebellar ataxia are the main characteristics of patients carrying the DNMT1 p.Y511H as compared with those carrying DNMT1 p.Y511C. Although HSAN1E and AD CA-DN are proposed to be called DNMT1-complex disorders owing to their overlapping symptoms, this finding suggests a distinct genotype–phenotype correlation regarding the DNMT1 p.Y511H and p.Y511C variants.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research

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The development of autoimmune antibody panels has improved the diagnosis of paraneoplastic neurological disorders (PNDs) of the brain and spinal cord. Here, we present a case of a woman with a history of breast cancer who presented with a subacute sensory ataxia that progressed over 18 months. Her examination and diagnostic studies were consistent with a myelopathy. Metabolic, infectious, and autoimmune testing were non-diagnostic. However, she responded to empirical immunosuppression, prompting further workup for an autoimmune etiology. An unbiased autoantibody screen utilizing phage display immunoprecipitation sequencing...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Conditions:   Hearing Loss;   Hearing Loss, Conductive;   Hearing Loss, Mixed;   Hearing Disorders;   Deafness;   Ear Diseases;   Otorhinolaryngologic Diseases;   Sensation Disorders;   Neurologic Manifestations;   Nervous System Diseases Interventions:   Device: Device A;   Device: Device B Sponsor:   Oticon Medical Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Neuropediatrics - Category: Neurology Authors: Tags: Short Communication Source Type: research
In conclusion, PVL is a common finding in children with syndromic and non-syndromic genetic HL undergoing vestibular evaluation prior to cochlear implantation. Improved understanding of the molecular physiology of vestibular hair cell dysfunction is important for clinical care as well as research involving vestibular hair cells in model organisms and in vitro models.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Source: Neurological Sciences - Category: Neurology Source Type: research
Conclusions: This family demonstrated progressive neurodegeneration beginning with isolated areas of executive dysfunction and leading to globally impaired cognition and dementia. Cognitive decline occurred in parallel with neurological deterioration. The cognitive profile is similar to case reports of other individuals with an allelic neurological phenotype, Hereditary Sensory Autonomic Neuropathy 1E, also caused by DNMT1 mutations. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Source: Neuropsychology - Category: Neurology Authors: Source Type: research
In this study, we describe a...
Source: Clinical Epigenetics - Category: Research Authors: Source Type: research
We report a case showing overlap of both of these syndromes plus associated clinical features of common variable immune deficiency, scleroderma and endocrinopathy that could also be mutation associated. ResultsOur patient was found to be heterozygous for a previously unreported frameshift mutation, c.1635_1637delCAA p.(Asn545del) in the DNMT1 gene exon 20. DiscussionThis case displays both the first frameshift mutation described in the literature which is associated with a phenotype with a high degree of overlap between HSAN1E and ADCA‚ÄźDN and early age of onset (c. 8 yrs). Our case is also of interest as the patie...
Source: Journal of the Peripheral Nervous System - Category: Neurology Authors: Tags: CASE REPORT Source Type: research
We present seven cases – a patient with a previously unreported DNMT1 mutation and a family with six members affected by a more classical DNMT1 syndrome. A 20-year-old patient with a history of common variable immune deficiency presented with sensory loss. He developed a syndrome of hereditary sensory and autonomic neuropathy (HSAN1E), cataplexy, cerebellar atrophy, deafness, and cutaneous manifestations of a scleroderma spectrum disorder. There was no family history. Genetic testing revealed the patient was heterozygous for a previously unreported in-frame deletion mutation, c.1635_1637delCAA p.(Asn545del) in the DN...
Source: Journal of Neurology, Neurosurgery and Psychiatry - Category: Neurosurgery Authors: Tags: Genetics, Immunology (including allergy), Brain stem / cerebellum, Sleep disorders (neurology), Sleep disorders, Disability, Ear, nose and throat/otolaryngology Thur 21, Parallel session 5: Therapeutics Source Type: research
We report a broader than previously appreciated clinical spectrum for hereditary sensory and autonomic neuropathy type 1E (HSAN1E) and a potential pathogenic mechanism for DNA methyltransferase (DNMT1) mutations. The clinical presentations and genetic characteristics of nine newly identified HSAN1E kinships (45 affected subjects) were investigated. Five novel mutations of DNMT1 were discovered; p.C353F, p.T481P, p.P491L, p.Y524D and p.I531N, all within the target-sequence domain, and two mutations (p.T481P, p.P491L) arising de novo. Recently, HSAN1E has been suggested as an allelic disorder of autosomal dominant cerebellar...
Source: Brain - Category: Neurology Authors: Tags: Original Articles Source Type: research
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