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

The phenotypes of patients with disease-associated variants in DNMT1 have been classified into two syndromes: hereditary sensory and autonomic neuropathy type 1E (HSAN1E, MIM614116, https://www.omim.org/ ) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN, MIM604121). The a...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2021-09, Vol.71 (9), p.1796-1801
Main Authors: Kikuchi, Junko Kanda, Nagashima, Yu, Mano, Tatsuo, Ishiura, Hiroyuki, Hayashi, Toshihiro, Shimizu, Jun, Matsukawa, Takashi, Ichikawa, Yaeko, Takahashi, Yuji, Karino, Shotaro, Kanbayashi, Takashi, Kira, Junichi, Goto, Jun, Tsuji, Shoji
Format: Article
Language:English
Subjects:
Aged
Amino acids
Ataxia
Autonomic nervous system
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cerebellar ataxia
Cerebellar Ataxia - genetics
Cerebellar Ataxia - pathology
Cerebellum
Deafness
DNA (Cytosine-5-)-Methyltransferase 1 - genetics
DNMT1 protein
Genotypes
Humans
Literature reviews
Male
Middle Aged
Mutation, Missense
Narcolepsy
Neurochemistry
Neurology
Neuropathy
Neurosciences
Patients
Pedigree
Phenotype
Phenotypes
Proteomics
Signs and symptoms
Sleep disorders
Citations: Items that this one cites
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Summary:The phenotypes of patients with disease-associated variants in DNMT1 have been classified into two syndromes: hereditary sensory and autonomic neuropathy type 1E (HSAN1E, MIM614116, https://www.omim.org/ ) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN, MIM604121). The amino acid codon 511 is a hotspot, and p.Y511C is the most frequently observed disease-associated variant among those in HSAN1E patients, whereas there have been only a few reports on patients with p.Y511H. In this study, we report on the cases of a kindred carrying the DNMT1 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 ADCA-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.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-020-01784-5