Chromosomal microarray (CMA) is now recognized as the first-tier genetic test for detection of copy number variations (CNVs) in patients with autism spectrum disorder (ASD). The aims of this study were to identify known and novel ASD associated-CNVs and to evaluate the diagnostic yield of CMA in Thai patients with ASD. The Infinium CytoSNP-850K BeadChip was used to detect CNVs in 114 Thai patients comprised of 68 retrospective ASD patients (group 1) with the use of CMA as a second line test and 46 prospective ASD and developmental delay patients (group 2) with the use of CMA as the first-tier test. We identified 7 (6.1%) pathogenic CNVs and 22 (19.3%) variants of uncertain clinical significance (VOUS). A total of 29 patients with pathogenic CNVs and VOUS were found in 22% (15/68) and 30.4% (14/46) of the patients in groups 1 and 2, respectively. The difference in detected CNV frequencies between the 2 groups was not statistically significant (Chi square = 1.02, df = 1, P = 0.31). In addition, we propose one novel ASD candidate gene, SERINC2, which warrants further investigation. Our findings provide supportive evidence that CMA studies using population-specific reference databases in underrepresented populations are useful for identification of novel candidate genes.

Fragile X syndrome (FXS) is the most common single gene disorder, which causes autism and intellectual disability. The fragile X mental retardation 1 (FMR1) gene is silenced when cytosine-guanine-guanine (CGG) triplet repeats exceed 200, which is the full mutation that causes FXS. Carriers of FXS have a CGG repeat between 55 and 200, which is defined as a premutation and transcription of the gene is overactive with high levels of the FMR1 mRNA. Most carriers of the premutation have normal levels of fragile X mental retardation protein (FMRP) and a normal intelligence, but in the upper range of the premutation (120-200) the FMRP level may be lower than normal. The clinical problems associated with the premutation are caused by the RNA toxicity associated with increased FMR1 mRNA levels, although for some mildly lowered FMRP can cause problems associated with FXS. The RNA toxicity causes various health problems in the carriers including but not limited to fragile X-associated tremor/ataxia syndrome, fragile X-associated primary ovarian insufficiency, and fragile X-associated neuropsychiatric disorders. Since some individuals with neuropsychiatric problems do not meet the severity for a diagnosis of a "disorder" then the condition can be labeled as fragile X premutation associated condition (FXPAC). Physicians must be able to recognize these health problems in the carriers and provide appropriate management.FMR1, fragile X premutation associated conditions, fragile X-associated neuropsychiatric disorders, fragile X-associated primary ovarian insufficiency, fragile X-associated tremor/ ataxia syndrome, premutation | INTRODUCTIONFragile X syndrome (FXS) is caused by mutations of the fragile X mental retardation 1 (FMR1) gene at Xq27.3. Almost all of the mutations (> 99%) are due to more than 200+ repeats of cytosine-guanine-guanine (CGG) in the FMR1 gene, which is called "full mutation." The CGG expansion leads to methylation at the promoter region of the FMR1 gene and transcriptional silencing which result in fragile X mental retardation protein (FMRP) deficiency. FMRP, which is abundant in neurons, is a regulatory protein in synaptogenesis. 1 The hallmarks of FXS are developmental delay, intellectual disability, and autism spectrum disorder (ASD). Elongated face, prominent and large ears, macrocephaly, and macroorchidism beginning at the pubertal period are also characteristic of FXS. A systematic review and meta-analysis reported that the prevalence of FXS is approximately 1:7143 in males and 1:11 111 in females. 2 In 1-2% of individuals with ASD, FXS was identified. 3 However, FXS is still underrecognized and the availability of fragile X DNA testing is limited, and thus the prevalence may be underestimated.Whenever FXS is diagnosed, fragile X premutation carriers should be sought in the proband's family. The premutation range is 55-200 CGG repeats in the FMR1 gene. In a systematic review and meta-analysis, premutation was detected at a rate of 1:855 in males and 1:291 in females, rates, which were more prevalent ...

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PurposeTo determine whether perioperative desaturation (PD) in preschool children undergoing non-cardiac surgery is associated with subsequent impairment of intelligence or subsequent change in age-specific weight and height percentile.MethodA historical-concurrent follow-up study was conducted in children aged ≤ 60 months who underwent general anesthesia (GA) for non-cardiac surgery between January 2008 and December 2011 at Songklanagarind Hospital. Children who developed PD (PD group) and children who did not develop perioperative respiratory events (no-PRE group) were matched on sex, age, year of having index GA, type of surgery and choice of anesthesia. The children’s age-specific weight and height percentile and intelligence quotient (IQ) scores by Standford Binet-LM or Wechsler Intelligence Scale for Children, 3rd edition 12–60 months after GA were compared using Student’s t- test and Wilcoxon’s rank sum test. Multivariate linear regression models for standardized IQ and multivariate mixed effects linear regression models for the change of age-specific weight and height percentile from the time of index GA to the time of IQ test were performed to identify independent predictors. The coefficients and 95% confidence intervals (CI) were displayed and considered significant if the F test p-values were < 0.05.ResultsOf 103 subjects in each group (PD vs no-PRE), there were no statistically significant differences in IQ (94.7 vs 98.3, p = 0.13), standardized IQ (−0.1 vs 0.1, p = 0.14) or age-specific weight percentile (38th vs 63th, p = 0.06). However, age-specific height percentile in the PD group at the time of IQ test was significantly lower (38th vs 50th, p = 0.02). In the multivariate analysis, PD was not a significant predictor for standardized IQ (coefficient: −0.06, 95% CI: −0.3, 0.19, p = 0.57), change in age-specific weight percentile (coefficient: 4.66, 95% CI: −2.63, 11.95, p = 0.21) or change in age-specific height percentile (coefficient: −1.65, 95% CI: −9.74, 6.44, p = 0.69) from the time of index GA to the time of IQ test after adjusting for family and anesthesia characteristics.ConclusionOur study could not demonstrate any serious effect of PD on subsequent intelligence or on the change in age-specific weight and height percentile of children after non-cardiac surgery.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-164) contains supplementary material, which is available to authorized users.

Objective To evaluate the effectiveness of parenting training on emotional and behavioral problems of first through fourth grade Thai children with ADHD compared with routine clinical care in a university hospital in southern Thailand. Material and methods Caregivers of the children were invited and assessed for eligibility. Eighty children with ADHD were randomly assigned to either a parenting training group or a routine clinical care group. The primary caregivers of the parenting training group participated in 6 120-minute weekly sessions in addition to routine clinical care. Caregiver and teacher ADHD ratings and oppositional-defiant disorder ratings were collected at the time of enrollment and after the 6 weeks of training in both groups. The differences in scores in both groups were analyzed using a mixed model ANOVA. Results Each arm had 40 participants. The mean (SD) age of the children was 8.3 (1.1) years and their mean (SD) age at the first diagnosis of ADHD was 6.8 (1.3) years. Most of them were receiving methylphenidate for treatment of their ADHD. The mother was the primary caregiver for 83.5% of the children. The ADHD symptoms and oppositional-defiant symptoms showed significant improvement after receiving the treatment in both groups; however, no significant differences were found between groups. Conclusion Adding parenting training to the routine clinical care for children with uncomplicated ADHD who are being medicated was not more effective than the routine clinical care alone. However, the power of this study is limited, and follow-up is needed to evaluate the long-term effectiveness.