Hereditary Sensory and Autonomic Neuropathy Type Ie

Last update 08 May 2025

Basic Info

Synonyms

Dnmt1-Related Dementia, Deafness, and Sensory Neuropathy, HSAN1E, HSN IE

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Introduction

A rare genetic neurological disorder characterized by sensorineural hearing loss, sensory neuropathy, behavioral abnormalities, and dementia. Occurrence of seizures has also been reported. Age of onset is between adolescence and adulthood. The disease is progressive, with fatal outcome typically in the fifth to sixth decade.

Clinical Trials associated with Hereditary Sensory and Autonomic Neuropathy Type Ie

NCT01793168

/ RecruitingNot Applicable

Coordination of Rare Diseases at Sanford

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

Start Date01 Jul 2010

Sponsor / Collaborator

Sanford Health Corp.

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100 Clinical Results associated with Hereditary Sensory and Autonomic Neuropathy Type Ie

100 Translational Medicine associated with Hereditary Sensory and Autonomic Neuropathy Type Ie

0 Patents (Medical) associated with Hereditary Sensory and Autonomic Neuropathy Type Ie

Literatures (Medical) associated with Hereditary Sensory and Autonomic Neuropathy Type Ie

01 Apr 2024·The International Journal of Biochemistry & Cell Biology

DNMT1 Y495C mutation interferes with maintenance methylation of imprinting control regions

Article

Author: Chaillet, John Richard ; Choudhury, Sumana ; Singh, Minali ; Anne, Anuhya ; Mohan, Kommu Naga

Hereditary Sensory and Autonomic Neuropathy Type 1E (HSAN1E) is a rare autosomal dominant neurological disorder due to missense mutations in DNA methyltransferase 1 (DNMT1). To investigate the nature of the dominant effect, we compared methylomes of transgenic R1^wtDnmt1 and R1^Dnmt1Y495C mouse embryonic stem cells (mESCs) overexpressing WT and the mutant mouse proteins respectively, with the R1 (wild-type) cells. In case of R1^Dnmt1Y495C, 15 out of the 20 imprinting control regions were hypomethylated with transcript level dysregulation of multiple imprinted genes in ESCs and neurons. Non-imprinted regions, minor satellites, major satellites, LINE1 and IAP repeats were unaffected. These data mirror the specific imprinting defects associated with transient removal of DNMT1 in mESCs, deletion of the maternal-effect DNMT1o variant in preimplantation mouse embryos, and in part, reprogramming to naïve human iPSCs. This is the first DNMT1 mutation demonstrated to specifically affect Imprinting Control Regions (ICRs), and reinforces the differences in maintenance methylation of ICRs over non-imprinted regions. Consistent with nervous system abnormalities in the HSAN1E disorder and involvement of imprinted genes in normal development and neurogenesis, R1^Dnmt1Y495C cells showed dysregulated pluripotency and neuron marker genes, and yielded more slender, shorter, and extensively branched neurons. We speculate that R1^Dnmt1Y495C cells produce predominantly dimers containing mutant proteins, leading to a gradual and specific loss of ICR methylation during early human development.

01 Jan 2024·Rinsho Shinkeigaku

Hereditary sensory and autonomic neuropathy 1E showing hyperreflexia: a case report

Article

Author: Takiyama, Yoshihisa ; Ikezoe, Koji ; Arita, Yukimasa ; Hayashida, Hitoshi ; Koh, Kishin

A 52-year-old man had developed hearing loss since childhood, as well as recurrent foot ulcers and osteomyelitis since his forties. He presented with gait disturbance and dysarthria that had worsened over four years and a month, respectively. Neurological exams revealed cognitive impairment, proximal weakness of the lower extremities, generalized hyperrflexia, ataxia, sensory disturbances predominant in deep sensation, urinary retention, and gait instability. On nerve conduction study, no sensory nerve action potentials were evoked in the upper and lower limbs. Since his grandmother suffered from similar symptoms, we investigated genetic analysis, which revealed a missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene. He was subsequently diagnosed with hereditary sensory and autonomic neuropathy 1E (HSAN1E). It is important to recognize that increased deep tendon reflex can be observed in HSAN1E.

01 Sep 2023·Journal of the Peripheral Nervous System

DNMT1‐associated sensory neuropathy and cerebellar ataxia: A novel variant and review of genotype–phenotype correlation

Author: Alexander, Michael D ; Crowley, Paul ; O'Dowd, Sean ; Murphy, Sinéad M ; Killeen, Ronan P ; Menon, Poornima Jayadev ; Bogdanova-Mihaylova, Petya ; McDermott, Garret

AbstractAimHereditary sensory neuropathy (HSN) 1E is a neurodegenerative disorder caused by pathogenic variants in DNA methyltransferase 1 (DNMT1). It is characterised by sensorineural deafness, sensory neuropathy and cognitive decline. Variants in DNMT1 are also associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy.MethodsA 42‐year‐old man presented with imbalance, lancinating pain, numerous paucisymptomatic injuries, progressive deafness since his mid‐20s, mild cognitive decline and apathy. Examination revealed abnormalities of eye movements, distal sensory loss to all modalities, areflexia without weakness and lower limb ataxia. MRI brain and FDG‐PET scan demonstrated biparietal and cerebellar atrophy/hypometabolism. Whole exome sequencing detected a heterozygous likely pathogenic missense variant in DNMT1, c.1289G > A, p.Cys430Tyr. Cochlear implant was performed at 44 years for the bilateral high frequency sensorineural hearing loss with improvement in hearing and day‐to‐day function.Results and ConclusionWe describe a novel variant in DNMT1 and confirm that an overlapping HSN1E‐cerebellar phenotype can occur. Only one prior case of cochlear implant in HSN1E has been reported to date but this case adds to that literature, suggesting that cochlear implant can be successful in such patients. We further explore the clinical and radiological signature of the cognitive syndrome associated with this disorder.

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