Abstract
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.
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Abbreviations
- MMSE:
-
Mini-Mental State Examination
- WAIS:
-
Wechsler Adult Intelligence Scale
- VIQ:
-
Verbal Intelligence Quotient
- PIQ:
-
Performance Intelligence Quotient
- FIQ:
-
Full-Scale Intelligence Quotient
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Acknowledgments
We thank the family members for participating in this study. We also thank the doctors who collected and provided clinical information of the patients.
Funding
This work was supported in part by Grants-in-Aid [H23-Jitsuyoka (Nanbyo)-Ippan-004 and H26-Jitsuyoka (Nanbyo)-Ippan-080] from the Ministry of Health, Labour and Welfare, Japan, and grants (16kk0205001h0003, 18ek0109279h0002, and 19ek0109279h0003) from the Japan Agency for Medical Research and development, AMED.
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Kikuchi, J.K., Nagashima, Y., Mano, T. et al. Cerebellar Ataxia as a Common Clinical Presentation Associated with DNMT1 p.Y511H and a Review of the Literature. J Mol Neurosci 71, 1796–1801 (2021). https://doi.org/10.1007/s12031-020-01784-5
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DOI: https://doi.org/10.1007/s12031-020-01784-5