Autosomal dominant cerebellar ataxia, deafness, and narcolepsy with amenorrhea, subclinical optic atrophy, and electroencephalographic abnormality: A case report
Hereditary cerebellar ataxia is a heterogeneous group of diseases. An accurate diagnosis of this disease is challenging for clinicians. Here, we report a patient with DNMT1 mutation who presented with mid-age onset of cerebellar ataxia, sensorineural hearing loss, and pyramidal signs. [Read full article]
Identification of a methylation profile for DNMT1-associated autosomal dominant cerebellar ataxia, deafness, and narcolepsy
Clinical Epigenetics, 2016, 8:91
DNA methylation is an essential epigenetic mark, controlled by DNA methyltransferase (DNMT) proteins, which regulates chromatin structure and gene expression throughout the genome. In this study, we describe a family with adult-onset autosomal dominant cerebellar ataxia with deafness and narcolepsy (ADCA-DN) caused by mutations in the maintenance methyltransferase DNMT1 and assess the DNA methylation profile of these individuals. [Read full article]
Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30–40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy–cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT1 as the only gene with mutations found in all five affected individuals. [Read full article]
Neurol Genet, 2020.
To report novel causal mutations, expanded clinical phenotypes, and clinical management of DNA methyltransferase 1 (DNMT1)-complex disorder. [Read full article]
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. [Read full article]
Genetics Home Reference, 2014.
The DNMT1 gene provides instructions for making an enzyme called DNA methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms (methylation), to DNA molecules. [Read full article]
Aberrant signature methylome by DNMT1 hot spot mutation in hereditary sensory and autonomic neuropathy 1E
DNA methyltransferase 1 (DNMT1) is essential for DNA methylation, gene regulation and chromatin stability. We previously discovered DNMT1 mutations cause hereditary sensory and autonomic neuropathy type 1 with dementia and hearing loss (HSAN1E; OMIM 614116). HSAN1E is the first adult-onset neurodegenerative disorder caused by a defect in a methyltransferase gene. [Read full article]
Hereditary sensory neuropathy type 1E is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early‑onset dementia (summary by Klein et al., 2011). [Read full article]
NCBI Bookshelf, 2013.
DNMT1-related dementia, deafness, and sensory neuropathy (HSAN IE) is a degenerative disorder of the central and peripheral nervous systems characterized by sensory impairment of the distal lower extremities, loss of sweating (sudomotor function) on the distal aspects of the upper and lower limbs, sensorineural hearing loss, and dementia. Affected persons are normal in their youth but begin to manifest progressive sensory neuropathy and moderate to severe progressive sensorineural deafness by age 20 to 35 years. [Read full article]
American Academy of Neurology, 2013.
Mutations in DNA methyltransferase 1 (DNMT1) have been identified in 2 autosomal dominant syndromes: 1) hereditary sensory autonomic neuropathy with dementia and hearing loss (HSAN1E); and 2) cerebellar ataxia, deafness, and narcolepsy. Both syndromes have mutations in targeting sequence (TS) domain (exons 20-21), which is important in mediating DNA substrate binding to the DNMT1 catalytic domain. [Read full article]
Genetics Home Reference, 2012.
Hereditary sensory and autonomic neuropathy type 1E (HSAN 1E) is a disorder that affects the nervous system. Affected individuals have a gradual loss of intellectual function (dementia), typically beginning in their thirties. In some people with this disorder, changes in personality become apparent before problems with thinking skills. [Read full article]
DNA methyltransferase 1 (DNMT1) is crucial for maintenance of methylation, gene regulation and chromatin stability. DNA mismatch repair, cell cycle regulation in post-mitotic neurons and neurogenesis are influenced by DNA methylation. Here we show mutations in DNMT1 cause both central and peripheral neurodegeneration in one form of hereditary sensory and autonomic neuropathy (HSAN1) with dementia and hearing loss. [Read full article]
Prevention Genetics, 2012.
Hereditary sensory neuropaihy type 1E (HSN1E, OMIM 614116) was first described in a multi-generation American family with adult-onset distal sensory impairment and subsequent progressive memory and sensorineural hearing loss. Onset of dementia occurred between the second and fourth decades of life and death occurred in the fifth and sixth decades of life. [Read full article]