Genetic and clinical profile of 15 Chinese families with GDAP1-related Charcot-Marie-Tooth disease and identification of H256R as a frequent mutation.

BACKGROUND AND AIMS: Mutations in ganglioside-induced differentiation-associated protein 1 (GDAP1) cause axonal or demyelinating Charcot-Marie-Tooth disease (CMT) with autosomal dominant or recessive inheritance. In this study, we aim to report the genotypic and phenotypic features of GDAP1-related CMT in a Chinese cohort. METHODS: Clinical, neurophysiological, genetic data, and available muscle/brain imaging information of 28 CMT patients with GDAP1 variants were retrospectively collected. RESULTS: We identified 16 GDAP1 pathogenic variants, among which two novel variants c.980dup(p.L328FfsX25) and c.480+4T>G were first reported. Most patients (16/28) presented with AR or AD CMT2K phenotype. Clinical characteristics in our cohort demonstrated that the AR patients presented earlier onset, more severe phenotype compared with the AD patients. Considerable intra-familial phenotypic variability was observed among three AD families. Muscle atrophy and fatty infiltration in the lower extremity were detected by Muscle magnetic resonance imaging (MRI) scans in four patients. MRI showed two AR patients showed more severe muscle involvement of the posterior compartment than those of the anterolateral compartment in the calf. One patient carrying Q38*/H256R variants accompanied with mild periventricular leukoaraiosis. CONCLUSIONS: In this study, we conducted an analysis of clinical features of the GDAP1-related CMT patients, expanded the mutation spectrum in GDAP1 by reporting two novel variants, and presented the prevalent occurrence of the H256R mutation in China. The screening of GDAP1 should be particularly emphasized in Chinese patients with CMT2, given the incomplete penetrance and pathogenic inheritance patterns involving dominant and recessive modes.

Effectiveness of internet-based nursing interventions for the treatment of patients with periodontitis.

BACKGROUND: Periodontitis, one of the most common oral diseases, is a chronic inflammatory condition occur in response to bacterial plaque biofilms. Plaque control and oral hygiene instructions are the most widely used and effective nonsurgical treatment for periodontitis, which is based on a partnership between patient and clinician and requires a life-long commitment. The objective of this study was to analyze the effectiveness of internet-based nursing interventions for the treatment of patients with periodontitis. The findings from this study may help to enhance the therapeutic outcomes for patients with periodontitis. METHODS: A total of 80 patients with periodontitis treated in Zhejiang Province Stomatology hospital from December 2021 to January 2023 were randomly selected and divided into control group and intervention group with 40 cases each. The control group was given routine oral health guidance and the intervention group received internet based nursing intervention. The periodontal pocket depth, percentage of periodontal pocket depth (PD) ≥ 4 mm, bleeding on probing (BOP)%, and self-efficacy scale for oral health care (SESS) were assessed and compared at four time points: initial visit, 6-8-weeks follow-up, 3-months follow-up, and 6-months follow-up. RESULTS: There was no significant difference between the two groups in terms of age, gender, initial visit PD, initial visit PD ≥ 4 mm (%), initial visit BOP (%), and initial visit SESS (P > 0.05). The intervention group showed a significantly decreased percentage of PD ≥ 4 mm at 6-8 weeks and 6-months follow-up compared to the control group (P < 0.05). The PD, BOP%, and SESS scores of the intervention group were significantly better than those of the control group at 6-months follow-up (P < 0.05). There was no statistically significant difference in patient satisfaction between the two groups. CONCLUSIONS: This study confirmed that the internet-based nursing intervention in conjunction with periodontal treatment was able to improve the periodontal pocket depth, gingival bleeding and the level of self-efficacy of patients, suggesting that it is necessary to carry out the extended oral hygiene instructions via internet-based platforms for the patients in clinical practice.

Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND AND AIMS: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID. METHODS: In this retrospective dual-center study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot-Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022. RESULTS: Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n = 27) and non-muscle weakness type (n = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%). INTERPRETATION: Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.

Impact of COVID-19 on patient follow-up during supportive periodontal therapy: a retrospective study based on phone call survey.

BACKGROUND: COVID-19 and the subsequent intermittent lockdown measures from 2020 to 2022 in China critically disrupted regular medical activities, including dental care. This study aimed to investigate the impact of COVID-19 on long-term follow-up at the Stomatology Hospital, Zhejiang University School of Medicine and to evaluate potential causes of loss to follow-up. METHODS: A total of 1062 patients with periodontitis who visited the hospital from January 2019 to June 2022 were included in this study, and patient information was collected retrospectively in the form of a telephone questionnaire. The questionnaire consisted of 19 questions in four areas: demographic characteristics, clinical periodontal parameters, oral hygiene habits, and follow-up-related open-ended questions (specific reasons for loss to follow-up, attitudes toward follow-up and suggestions for increasing participation in future follow-ups). Regression analysis of factors influencing the follow-up of patients with periodontitis were analyzed by regression analysis using R (v4.2.3) software. RESULTS: A total of 536 (50.47%) valid questionnaires were collected from 1062 patients. Personal factors (42.5%), instead of the COVID-19 epidemic (20.0%), were the main factors that impacted the loss to follow-up in long-term periodontal treatment, while work factors (19.8%), hospital factors (16.4%), and transportation or distance factors (14.7%) were all important factors. A family history of periodontitis [odds ratio (OR) = 0.567, 95% confidence interval (CI): 0.393, 0.817, p = 0.002], as well as frequent use of dental devices (OR = 0.540, 95% CI: 0.375, 0.777, p = 0.001), were significantly associated with a "negative" attitude toward follow-up visits. CONCLUSION: This survey suggests that the COVID-19 epidemic factor was an important cause contributed to the loss to follow-up during supportive periodontal therapy (SPT) among a variety of potential factors. Majority of patients had negative attitudes toward subsequent continued participation in supportive care.

Genotype and phenotype distribution of 435 patients with Charcot-Marie-Tooth disease from central south China.

BACKGROUND AND PURPOSE: The purpose was to provide an overview of genotype and phenotype distribution in a cohort of patients with Charcot-Marie-Tooth disease (CMT) and related disorders from central south China. METHODS: In all, 435 patients were enrolled and detailed clinical data were collected. Multiplex ligation-dependent probe amplification for PMP22 duplication/deletion and CMT multi-gene panel sequencing were performed. Whole exome sequencing was further applied in the remaining patients who failed to achieve molecular diagnosis. RESULTS: Among the 435 patients, 216 had CMT1, 14 had hereditary neuropathy with pressure palsies (HNPP), 178 had CMT2, 24 had distal hereditary motor neuropathy (dHMN) and three had hereditary sensory and autonomic neuropathy (HSAN). The overall molecular diagnosis rate was 70%: 75.7% in CMT1, 100% in HNPP, 64.6% in CMT2, 41.7% in dHMN and 33.3% in HSAN. The most common four genotypes accounted for 68.9% of molecular diagnosed patients. Relatively frequent causes were missense changes in PMP22 (4.6%) and SH3TC2 (2.3%) in CMT1; and GDAP1 (5.1%), IGHMBP2 (4.5%) and MORC2 (3.9%) in CMT2. Twenty of 160 detected pathogenic variants and the associated phenotypes have not been previously reported. Broad phenotype spectra were observed in six genes, amongst which the pathogenic variants in BAG3 and SPTLC1 were detected in two sporadic patients presenting with the CMT2 phenotype. CONCLUSIONS: Our results provided a unique genotypic and phenotypic landscape of patients with CMT and related disorders from central south China, including a relatively high proportion of CMT2 and lower occurrence of PMP22 duplication. The broad phenotype spectra in certain genes have advanced our understanding of CMT.

Community structure and succession regulation of fungal consortia in the lignocellulose-degrading process on natural biomass.

The study aims to investigate fungal community structures and dynamic changes in forest soil lignocellulose-degrading process. rRNA gene clone libraries for the samples collected in different stages of lignocellulose degradation process were constructed and analyzed. A total of 26 representative RFLP types were obtained from original soil clone library, including Mucoromycotina (29.5%), unclassified Zygomycetes (33.5%), Ascomycota (32.4%), and Basidiomycota (4.6%). When soil accumulated with natural lignocellulose, 16 RFLP types were identified from 8-day clone library, including Basidiomycota (62.5%), Ascomycota (36.1%), and Fungi incertae sedis (1.4%). After enrichment for 15 days, identified 11 RFLP types were placed in 3 fungal groups: Basidiomycota (86.9%), Ascomycota (11.5%), and Fungi incertae sedis (1.6%). The results showed richer, more diversity and abundance fungal groups in original forest soil. With the degradation of lignocellulose, fungal groups Mucoromycotina and Ascomycota decreased gradually, and wood-rotting fungi Basidiomycota increased and replaced the opportunist fungi to become predominant group. Most of the fungal clones identified in sample were related to the reported lignocellulose-decomposing strains. Understanding of the microbial community structure and dynamic change during natural lignocellulose-degrading process will provide us with an idea and a basis to construct available commercial lignocellulosic enzymes or microbial complex.