ABSTRACT
Objective To evaluate the application value of whole exome sequencing (WES) in diagnosis of NDDs (neuro-developmental disorders) children.Metheod WES was used for the diagnosis of 35 unexplained NDD children, which admitted to the outpatient and ward of Children′s hospital affiliated to Capital institute of pediatric from November 2015 to November 2016.These children′s clinical data was collected detailedly.Using bioinformatics software tools combining with patient′s phenotype, the candidate genetic/genomic variants of these patients were identified from WES data.The final pathogenicity of genetic/genomic variants was interpreted according to the guideline of the American College of Medical Genetics and Genomics (ACMG), meanwhile, the variants validation and co-separation analysis in the parents and their family members were performed by Sanger sequencing, real time-PCR and multiplex ligation-dependent probe amplification (MLPA).Results 14 pathogenic single nucleotide variants (SNVs) and three pathogenic copy number variations (CNVs) were detected in the 35 NDD children, the detection rate in this study is 48.6%.Among the 14 pathogenic SNVs, 11 of them are the definite NDD-related genes according to OMIM database (such as CHARGE syndrome, Wiedemann-Steiner syndrome, Cockayne syndrome, etc.), and six of them are de novo (6/11, 54.6%).Three pathogenic CNVs were identified from WES data, including two microduplications and one microdeletion.Meanwhile, a female child carrying a frame shift mutation in MECP2 was found and the germline mosaicism with low-frequency mutation of this site (8.4%) was confirmed by his father's sperm.Conclusions The diagnosis rate of WES in NDDs children is 48.6% in our small-sample study.In addition to pathogenic/likely pathogenic SNVs, CNVs can be detected successfully from WES data, which effectively improved the diagnosis yield in NDDs children.
ABSTRACT
Objective To investigate the sleep structure of children with attention deficit hyperactivity disorder (ADHD) and the differences among subtypes of ADHD.Methods Ninety children with ADHD were diagnosed in Department of Neurology, the Children's Hospital Affiliated to Capital Institute of Pediatrics between June 2012 and June 2013, including 75 boys and 15 girls,6-14 years old [(9.5 ± 2.4) years old], and among them there were 55 cases of ADHD-combined type, 25 cases of ADHD-inattentive type, and 10 cases of ADHD-hyperactive impulsive type.Thirty healthy children whose age and sex matched with ADHD group,came from Beijing and the surrounding area,were selected as the healthy control group,including 23 boys and 7 girls,6-14 years old [(9.2 ± 2.9) years old].Two groups underwent full overnight sleep assessment.Results The latency of rapid eye movement(REM) in children with ADHD was (146.58 ± 47.28) minutes, and the sleep latency was 19.00 minutes [(8.25-37.50) minutes];while the latency of REM in healthy control group was (87.55-± 13.59) minutes, and the sleep latency was 9.00 minutes [(3.50-13.63)minutes].Compared with healthy control group, children with ADHD demonstrated the increased latency REM and sleep latency, and decreased sleep efficiency,the increasing times of awakening and total duration,and these differences were all statistically significant(all P ＜ 0.05).The percentage of non-rapid eye movement(NREM) phase Ⅱ in ADHD hybrid was lower than the ADHD attention-deficit(t =2.012,P ＜ 0.05).Sleep latency in ADHD attention-deficit was longer than the ADHD hybrid(t =2.964,P ＜ 0.05).No statistical differences were found among the various types in other indicators.The prevalence of periodic limb movements in sleep(PLMS) was 27.78％ (25/90 cases) in ADHD group and the prevalence of PLMS was 3.30％ (1/30 cases) in the healthy control group.The differences in prevalence between 2 groups were statistically significant (x2 =8.053, P ＜ 0.05).Conclusions Children with ADHD significantly display more problems with sleep.Sleep latency and NREM Ⅱ are different between ADHD attention-deficit and ADHD hybrid.