The Value of a Comprehensive Genomic Evaluation in Prenatal Diagnosis of Genetic Diseases: A Retrospective Study.

Currently, there are still many challenges in prenatal diagnosis, such as limited or uncertain fetal phenotyping, variant interpretation, and rapid turnaround times. The aim of this study was to illustrate the value of a comprehensive genomic evaluation in prenatal diagnosis. We retrospectively reviewed 20 fetuses with clinically significant copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) and no further exome sequencing testing in our tertiary center between 2019 and 2020. The residual DNA from the prenatal cases was used for the parallel implementation of CNV sequencing (CNV-seq) and trio-based clinical exome sequencing (trio-CES). CMA revealed 26 clinically significant CNVs (18 deletions and eight duplications) in 20 fetuses, in which five fetuses had two or more CNVs. There were eight fetuses with pathogenic CNVs (e.g., del 1p36), nine fetuses with likely pathogenic CNVs (e.g., dup 22q11.21), and three fetuses with variants of unknown significance (VOUS, e.g., dup 1q21.1q21.2). Trio-CES identified four fetuses with likely pathogenic mutations (SNV/InDels). Of note, a fetus was detected with a maternally inherited hemizygous variant in the SLX4 gene due to a 16p13.3 deletion on the paternal chromosome. The sizes of CNVs detected by CNV-seq were slightly larger than that of the SNP array, and four cases with mosaic CNVs were all identified by CNV-seq. In conclusion, microdeletion/duplication syndromes and monogenic disorders may co-exist in a subject, and CNV deletion may contribute to uncovering additional recessive disease alleles. The application of a comprehensive genomic evaluation (CNVs and SNV/InDels) has great value in the prenatal diagnosis arena. CNV-seq based on NGS technology is a reliable and a cost-effective technique for identifying CNVs.

[Familial clustering of obesity and the role of lifestyle factors among children in Beijing].

OBJECTIVE: To investigate the correlation between lifestyle factors, parental obesity and adiposity in children, in order to provide theoretical evidence for public health policy establishment. METHODS: A cross-sectional observation study was conducted among approximately 20 thousand children aged 2 - 18 years old in urban and rural regions of Beijing, by using stratified randomization clustering sampling methods. Familial environmental risk factors of children adiposity and parental obesity were assessed with standardized questionnaire. Anthropometric measurements, including height and weight, were conducted. SPSS 13.0 software was applied to analyze the data, including general description, chi(2) trend test and non-condition logistic analyse. RESULTS: With IOTF obesity references, the prevalence of obesity in 21,198 children aged 2 - 18 years old was 5.6%. The behavioral characters (for example, smoking and drinking) and children obesity showed significant familial aggregation. In groups including "both parents not smoke", "only one parent smoke" and "both parents smoke", the smoking rates of offsprings were 1.50%, 2.93% and 6.01%, respectively (chi(trend)(2) = 107.009, P < 0.01). A similar pattern was found for offsprings' alcohol consumption rates (5.85%, 9.12% and 13.96%; chi(trend)(2) = 107.009, P < 0.01). Based on parents' BMI status, in groups including "both parents had normal weight", "father was obese", "mother was obese" and "both parents were obese", the prevalence of obesity in children were 3.29%, 11.48%, 9.12% and 27.01%, respectively (chi(trend)(2) = 293.404, P < 0.01). After controlling for sex and ages, factors such as physical exercises, sleeping times per day, fat intakes, watching TV, drinking alcohol were impact factors of children obesity. After controlling of confounding factors, such as children gender, age, birth weight, puberty, smoking history, drinking history, fat intakes, soft drink, physical exercises, education experiences of parents, smoking history, drinking history, family income and so on, maternal obesity had a greater influence on daughters than on sons (OR = 5.93, 95% CI: 3.57 - 9.84), and paternal obesity showed similar influence on sons (OR = 4.29, 95% CI: 3.21 - 5.72). Comparing to parents with normal weight, obese parents had more powerful impact on daughters (OR = 28.51, 95% CI: 15.13 - 53.72) than on sons (OR = 7.21, 95% CI: 4.07 - 12.75), regarding to 2 - 5 years group and 10 - 12 years group versus other age group (OR = 18.67, 95% CI: 1.49 - 234.46; OR = 22.25, 95% CI: 10.62 - 46.59). CONCLUSION: Parental obesity is an independent risk factor of adiposity in children; gender and age affect this association. The lifestyle patterns of parents should have great impact on children. When prevention or intervention with children obesity, familial environmental factors should be emphasized.