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Background: DNA methyltransferase 1 (EC 2.1.1.37), encoded by DNMT1 gene, is one of key enzymes in maintaining DNA methylation patterns of the human genome. It plays a crucial role in embryonic development, imprinting and genome stability, cell differentiation. The dysfunction of this group of enzymes can lead to a variety of human genetic disorders. Until now, mutations in DNMT1 have been found to be associated with two distinct phenotypes. Mutations in exon 20 of this gene leads to hereditary sensory and autonomic neuropathy type IE, and mutations in exon 21 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy.Case Presentation: Here we report a novel DNMT1 mutation in a sporadic case of a Chinese patient with cerebellar ataxia, multiple motor and sensory neuropathy, hearing loss and psychiatric manifestations. Furthermore, we elucidated its pathogenic effect through molecular genetics studies and revealed that this defective DNMT1 function is responsible for the phenotypes in this individual.Conclusion: Our findings expand the spectrum of DNMT1-related disorders and provide a good example of precision medicine through the combination of exome sequencing and clinical testing. [ABSTRACT FROM AUTHOR]

Objectives: To compare the serum levels of high mobility group box chromosomal protein 1 (HMGB1) between patients with AS and healthy controls, and evaluate its association with disease activities and functional abilities; to investigate the cell surface receptors related to HMGB1 in AS patients., Methods: The HMGB1 serum levels from71 previously untreated AS patients and 40 healthy controls were detected by ELISA method. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), erythrocytesedimentationrate (ESR), and C-reactive protein (CRP) levels were assessed on these participants. The mRNA expression of HMGB1 and its relevant cell surface receptors RAGE, TLR2, TLR4, and IL-1Racp complex were analysed by RT-PCR., Results: The HMGB1 serum levels from AS patients were significantly higher than those from healthy controls and remarkably positive correlated with BASDAI, ASDAS, BASFI, CRP, and ESR. ASDAS showed more correlated to HMGB1 serum levels than BASDAI. Besides, the expression of TLR2, TLR4, and IL-1Racp from PBMCs revealed significant correlations with the expression of HMGB1., Conclusions: HMGB1 might be a good laboratory index for the evaluation of disease activities and disease severity in AS patients. Further, extracellular HMGB1 play its inflammatory role mainly via the expression of cell surface receptors TLR2, TLR4 and IL-1RAcP complex.