Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings

Abstract

Background Deletion and duplication of the 3.7 Mb region in 17p11.2 result in two syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study was to determine the prevalence, genetic characteristics and clinical phenotypes of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects. Methods 7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification P245 assay. 7319 fetuses with potential congenital defects were tested using next generation sequencing technique. Results 417 of 7077 pediatric patients were determined to carry chromosome imbalance. 28 (28/7077, 0.4%) cases had imbalance at chromosome 17p11.2. Among them, 12 cases (42.9%) had heterozygous deletions and 16 cases (57.1%) had heterozygous duplications. The clinical phenotypes were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations. Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with duplication had cerebral ventricle dilation. Conclusion Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.

Higher scores on autonomic symptom scales in pediatric patients with neurodevelopmental disorders of known genetic etiology

“…Previous research has also investigated distinct autonomic symptoms (i.e., gastrointestinal problems and sleep disturbances assessed via parent-report), in conjunction with core features of ASD, as a possible way to stratify clinically meaningful subgroups (Unwin et al, 2013). However, in the current investigation and based on the high inter-correlations between PASS subscales (see Table S4 and atypical function in various organ systems regulated by the ANS (Cappuccio et al, 2016;Daghsni et al, 2018;Lecavalier et al, 2019;Robinson et al, 2016;Talkowski et al, 2011;Zhang et al, 2021).…”

“…Advances in clinical genomic testing have identified numerous pathogenic variants causative for ASD and other complex neurodevelopmental and psychiatric phenotypes; however, characterization of variants of uncertain significance and the discovery of genes and mechanistic pathways connected to neural, cognitive, and biological processes are ongoing (De Rubeis et al., 2014 ; Iossifov et al., 2014 ). Genetic variants associated with ASD also confer risk for other neuropsychiatric conditions, medical problems, and other diseases (i.e., ataxias, altered growth patterns, hearing and/or visual impairments) and atypical function in various organ systems regulated by the ANS (Cappuccio et al., 2016 ; Daghsni et al., 2018 ; Lecavalier et al., 2019 ; Robinson et al., 2016 ; Talkowski et al., 2011 ; Zhang et al., 2021 ). The continued study and characterization of symptom dimensions that may be transdiagnostic is an important next step in understanding the underlying biology of known and emerging genetic disorders with complex neurodevelopmental phenotypes (Savatt & Myers, 2021 ; Srivastava et al., 2019 ).…”