OBJECTIVE: To explore the genotype-phenotype correlation in a Charcot-Marie-Tooth type 2A2A (CMT2A2A) pedigree and to provide genetic counseling for its subsequent pregnancies. METHODS: A Chinese pedigree presenting with "lower limb muscle atrophy and movement disorders" at the Prenatal Diagnosis Center of Xuzhou Central Hospital between January and August 2024 was selected as the study subject. Relevant clinical data were collected from the pedigree members. Peripheral blood samples from affected individuals, and amniotic fluid and/or chorionic villus samples were obtained for DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. Pathogenicity assessment and bioinformatic analysis were conducted. This study was approved by the Medical Ethics Committee of Xuzhou Central Hospital (Ethics No. XZXY-LK-20240111-0019). RESULTS: All affected individuals in this pedigree were females, whom included the proband, her mother, and her first daughter. Earlier age of onset was associated with more severe lower limb atrophy. A heterozygous missense variant of the MFN2 gene, namely c.314C>T (p.Thr105Met), was identified in the proband, her mother, daughter, and the third fetus from a re-marriage. The same variant was absent in her elder brother, current husband, and her fourth fetus. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG) and recommendations from Clinical Genome Resources (ClinGen), the variant was classified as pathogenic (PP1_Strong+PM1+PS3+PS4_Moderate+PP3_Moderate+PM2_Supporting). Analyses with PROVEAN and Mutation Taster had categorized the variant as "deleterious" and "disease-causing", respectively. Analysis with Uniprot and Jalview showed that the affected amino acid residue is conserved across multiple species. ChEBI software predicted that the variant may alter the polarity of the 105th amino acid residue. CONCLUSION The c.314C>T (p.Thr105Met) missense variant of the MFN2 gene probably underlie the CMT2A2A in this pedigree. Above finding has enabled prenatal diagnosis and genetic counseling for its subsequent pregnancies.
Adult ; Female ; Humans ; Male ; Charcot-Marie-Tooth Disease/genetics* ; East Asian People/genetics* ; Exome Sequencing ; Genetic Testing/methods* ; GTP Phosphohydrolases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation, Missense ; Pedigree

Objective To investigate the effects of moderate-intensity aerobic exercise intervention and its influencing factors in patients with Alzheimer's disease(AD).Methods Ninety-eight AD patients were randomly assigned into exercise group(50 cases)and control group(48 cases).The exercise group received moderate-intensity aerobic training for 3 months.Cognitive function was assessed using the MMSE and the AD assessment scale-cognitive subscale(ADAS-cog)at baseline,3 months and 6 months.Daily living abilities was evaluated by the AD cooperative study-activities of daily living scale(ADCS-ADL),behavioral symptoms was assessed by the neuropsychiatric Inventory(NPI)and life quality was measured by quality of life in AD(QOL-AD).The difference between 3 months and baseline ADAS-cog(ADAS-cog3-0)score was used as the dependent variable,multiple-factor linear regression was performed to analyze whether baseline characteristics of patients would affect the efficacy of exercise.Patients with an improvement of ≥4 points in ADAS-cog3-0 were classified into good prognosis group,and the others were classified into non-good prognosis group.Variables with P＜0.05 in the multiple-factor linear regression analysis were included in Logistic regression analysis to determine the best cutoff value through ROC curve.Results Compared with the control group,the exercise group showed a significant increase in MMSE and QOL-AD scores at 3 and 6 months,a significant decrease in ADAS-cog score at 3 and 6 months,a significant increase in ADCS-ADL score at 3 months,and a significant decrease in NPI score at 3 months(all P＜0.05).However,there was no significant difference between the two groups in ADCS-ADL and NPI scores at 6 months.Regression analysis showed that baseline MMSE score had a negative impact on cognitive function improvement in the exercise group,while age,gender,education level,ischemic symptoms,baseline activities of daily living,behavioral and psychological symptoms,and quality of life had no impact.Sensitivity and specificity analysis showed that aerobic exercise was more effective in AD patients with an MMSE score＞21.5 points,and aerobic exercise was still effective but had moderate effects in patients with an MMSE score below this cutoff.Conclusions Aerobic exercise has a significant improvement on cognitive function,activities of daily living,behavioral and psychological symptoms,and quality of life in AD patients.The better the cognitive level is preserved in AD patients,the better the short-term effects of aerobic exercise are.

OBJECTIVETo analyze the correlation between the genotype and phenotype of 18q deletion syndrome with chromosome microarray analysis (CMA).

METHODSEight cases with 18q deletion syndrome were selected, including two affected fetuses and six children patients. DNA was extracted and hybridized with Affymetrix CytoScan TM 750K arrays following the manufacturer's standard protocol. The data was analyzed with a special software package.

RESULTSCMA analysis identified pathogenic copy number variations (CNVs) on 18q in all cases, which ranged from 6.612 Mb to 22.973 Mb. NFATC1, GALR1, MBP, SALL3 and TSHZ1 are likely to be causative genes for congenital heart disease, psychological, growth retardation, and cleft palate.

CONCLUSIONCMA can precisely locate the breakpoints of 18q and facilitate definition of the genotype-phenotype correlations, which is useful for prognosis.

Child, Preschool ; Chromosome Deletion ; Chromosome Disorders ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Infant ; Male ; Microarray Analysis