ABSTRACT
OBJECTIVE@#To assess the diagnostic value of whole exome sequencing (WES) for patients with intellectual disability (ID) or global developmental delay (GDD).@*METHODS@#134 individuals with ID or GDD who presented at Chenzhou First People's Hospital between May 2018 and December 2021 were selected as the study subjects. WES was carried out on peripheral blood samples of the patients and their parents, and candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq) and co-segregation analysis. The pathogenicity of the variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#A total of 46 pathogenic single nucleotide variants (SNVs) and small insertion/deletion (InDel) variants, 11 pathogenic genomic copy number variants (CNVs), and 1 uniparental diploidy (UPD) were detected, which yielded an overall detection rate of 43.28% (58/134). The 46 pathogenic SNV/InDel have involved 62 mutation sites in 40 genes, among which MECP2 was the most frequent (n = 4). The 11 pathogenic CNVs have included 10 deletions and 1 duplication, which have ranged from 0.76 to 15.02 Mb. A loss of heterozygosity (LOH) region of approximately 15.62 Mb was detected in 15q11.2q12 region in a patient, which was validated as paternal UPD based on the result of trio-WES. The patient was ultimately diagnosed as Angelman syndrome.@*CONCLUSION@#WES can detect not only SNV/InDel, but also CNV and LOH. By integrating family data, WES can accurately determine the origin of the variants and provide a useful tool for uncovering the genetic etiology of patients with ID or GDD.
Subject(s)
Humans , Exome Sequencing , Intellectual Disability/genetics , DNA Copy Number Variations , Mutation , Loss of HeterozygosityABSTRACT
Objective To evaluate the value of chromosomal microarray analysis (CMA) for genetic evaluation of fetal ultrasound abnormality. Methods A total of 180 pregnant women with fetal abnormality detected by prenatal ultrasound diagnosis in the first trimester during the period from January 2020 through May 2022 were enrolled as the study subjects. All prenatal fetal screening samples were subjected to G-band karyotyping and CMA. Results G-band karyotyping detected normal karyotypes in 168 samples (93.85%) and abnormal karyotypes in 11 samples (6.15%), and CMA detected 17 positive samples (9.44%) and 163 negative samples (90.56%). The seventeen positive samples included 11 pathogenic copy number variations (CNVs) and 6 variants of unknown significance (VOUS), and there were 11 CMA-positive results consistent with G-band karyotyping, and 6 additional pathogenic CNVs mainly included microdeletion and microduplication syndromes. The detection rates of pathogenic CNVs were 11.11%, 2.63%, 2.78%, 4.00%, 0, 0, 11.11% and 0 among the fetuses with abnormal structure of the cardiovascular system, the lymphatic system, the nervous system, the digestive system, the cranial and face system, the skeletal system, the urinary system, and other system (χ2 =8.188, P = 0.316). All eleven fetuses with pathogenic CNVs detected by CMA were all induced for abortion. Conclusion CMA improves the detection of genetic abnormality among fetuses with ultrasound abnormality in relative to G-band karyotyping, which is feasible for prenatal cytogenetic diagnosis among fetuses with ultrasound abnormality
ABSTRACT
Objective To study the efficacy and safety of different doses of caffeine citrate and aminophylline treatment for apnea of prematurity. Methods Preterm infants who met the inclusive criteria were admitted to NICU of JingZhou Central Hospital from October 1st, 2013 to October 1st, 2015. They were randomly assigned to three groups. Infants assigned to high dose caffeine group were received a loading dose of 40 mg / kg daily, followed by the maintaining dose of 20 mg / kg daily. Neonates in low dose caffeine group were administered with the loading dose of 20 mg / kg daily, followed by maintaining dose of 10 mg / kg daily. Infants in the aminophylline group received a loading dose of 5 mg / kg, then with maintaining dose of 2 mg / kg every 12 hours. Caffeine citrate or aminophylline therapy were continued until the infants were free from apnea for a period of 7 days or when the gestational age of 34 weeks were reached. Extubation failure rate, frequency of apnea, duration of apnea, mechanical ventilation, as well as oxygen therapy, length of hospital stay, mortality, and the adverse effects were compared among three groups. Results 90 infants were enrolled for study, with 30 in each group. Extubation failure rate, frequency of apnea, apnea duraion and oxygen therapy duration of infants in high dose caffeine groups were all significantly lower than those of infants in low dose caffeine group and aminophylline group (P 0. 05). Duration of mechanical ventilation and CPAP, length of hospital stay, incidence of complications (BPD, ROP, IVH, PVL, NEC ), mortality were of no significant difference among three groups ( P > 0. 05 ) . Conclusions High dose caffeine therapy for apnea of prematurity is more effective in decreasing incidence of extubation failure and apnea, as well as decreasing duration of apnea and oxygen therapy. Tachycardia is the only adverse effect of high dose caffeine therapy discovered by this study.