Identification of a novel DNMT1 mutation in a Chinese patient with hereditary sensory and autonomic neuropathy type IE.

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.

Gut microbiota in patients with Parkinson's disease in southern China.

INTRODUCTION: Accumulating evidence has revealed alterations in the communication between the gut and brain in patients with Parkinson's disease (PD), and previous studies have confirmed that alterations in the gut microbiome play an important role in the pathogenesis of numerous diseases, including PD. The aim of this study was to determine whether the faecal microbiome of PD patients in southern China differs from that of control subjects and whether the gut microbiome composition alters among different PD motor phenotypes. METHODS: We compared the gut microbiota composition of 75 patients with PD and 45 age-matched controls using 16S rRNA next-generation-sequencing. RESULTS: We observed significant increases in the abundance of four bacterial families and significant decreases in the abundance of seventeen bacterial families in patients with PD compared to those of the controls. In particular, the abundance of Lachnospiraceae was reduced by 42.9% in patients with PD, whereas Bifidobacteriaceae was enriched in patients with PD. We did not identify a significant difference in the overall microbial composition among different PD motor phenotypes, but we identified the association between specific taxas and different PD motor phenotypes. CONCLUSIONS: PD is accompanied by alterations in the abundance of specific gut microbes. The abundance of certain gut microbes was altered depending on clinical motor phenotypes. Based on our findings, the gut microbiome may be a potential PD biomarker.

New eremophilane-type sesquiterpenes from an Antarctic deepsea derived fungus, Penicillium sp. PR19 N-1.

Chemical investigation of an Antarctic deepsea derived fungus Penicillium sp. PR19 N-1 yielded five new eremophilane-type sesquiterpenes 1­5 and a new rare lactam-type eremophilane 6, together with three known compounds 7­9. The structures of these diverse sesquiterpenes were determined by extensive NMR and mass spectroscopic analyses. Compounds 1, 2, 4­6, 8 and 9 were evaluated for their cytotoxities against HL-60 and A-549 human cancer cell lines, and 5 was the most active one with IC50 value of 5.2 lM against the A-549 cells.

Four new chloro-eremophilane sesquiterpenes from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1.

A new chloro-trinoreremophilane sesquiterpene 1, three new chlorinated eremophilane sesquiterpenes 2-4, together with a known compound, eremofortine C (5), were isolated from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1. Structures were established using IR, HRMS, 1D and 2D NMR techniques. In addition, the plausible metabolic network of these isolated products is proposed. Compound 1 showed moderate cytotoxic activity against HL-60 and A549 cancer cell lines.

Structural determination of aspericins A-C, new furan and pyran derivates from the marine-derived fungus Rhizopus sp. 2-PDA-61, by 1D and 2D NMR spectroscopy.

Three new furan and pyran derivatives named aspericins A-C (1-3), as well as a known asperic acid (4), have been isolated from the marine-derived fungus Rhizopus sp. 2-PDA-61. The complete (1)H and (13)C NMR assignments for the new compounds were carried out using (1)H, (13)C, DEPT, COSY, HMQC, HMBC, and NOESY NMR experiments. Compounds 1-3 were evaluated for their cytotoxic activities on P388, A549, HL-60, and BEL-7420 cell lines by the MTT and SRB methods.

A new diketopiperazine alkaloid isolated from an algicolous Aspergillus flavus strain.

A new diketopiperazine alkaloid containing the uncommon amino acid L-7, 9-dihydroxy-8-methoxyphenylalanine (1), has been isolated from the algicolous Aspergillus flavus strain. The structure of 1 including the absolute stereochemistry was determined by spectroscopic data and chemical means. Compound 1 showed weak cytotoxicity against HL-60 cell lines with an IC50 value of 36.5 microg/ml.

Two new 5-hydroxy-2-pyrone derivatives isolated from a marine-derived fungus Aspergillus flavus.

Two new compounds, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (1) and (5-hydroxy-2-oxo-2H-pyran-4-yl) methyl acetate (2), have been isolated from a marine-derived fungus Aspergillus flavus. Their structures were determined by spectroscopic data. Compound 1 induced the production of cAMP on GPR12 transfected CHO and HEK293 cells in a dose-dependent manner, which indicated 1 might be a possible ligand for GPR12.

Six new ergosterols from the marine-derived fungus Rhizopus sp.

Six new ergosterols, including 3beta-hydroxyl-(22E, 24R)-ergosta-5,8,22-trien-7,15-dione (1), 3beta-hydroxyl-(22E, 24R)-ergosta-5,8,14,22-tetraen-7-one (2), 3beta,15beta-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-one (3), 3beta,15alpha-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-one (4), 3beta-hydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7,15-dione (5), and 5alpha,8alpha-epidioxy-23,24(R)-dimethylcholesta-6,9(11),22-trien-3beta-ol (6), have been isolated from the marine-derived fungus Rhizopus sp., along with four known ones (7-10). The structures of the new compounds were determined on the basis of extensive spectroscopic data. All compounds were evaluated for their cytotoxic activities on P388, A549, HL-60, and BEL-7420 cell lines by the MTT and SRB methods.