Abstract
Objective: Intellectual disability (ID) is one of the most common developmental disabilities. To identify the genetic etiology of IDs in Chongqing, we conducted a multistage study in Chinese Han patients. Methods: We collected the clinical and etiological data of 1665 ID patients, including 1,604 from the disabled children evaluation center and 61 from the pediatric rehabilitation unit. Routine genetic screening results were obtained, including karyotype and candidate gene analysis. Then 105 idiopathic cases with syndromic and severe ID/developmental delay (DD) were selected and tested by chromosomal microarray (CMA) and whole exome sequencing (WES) sequentially. The pathogenicity of the CNVs and SNVs were evaluated according to ACMG guidelines. Results: Molecular diagnosis was made by routine genetic screening in 216 patients, including 196 chromosomal syndromes. Among the 105 idiopathic patients, 49 patients with pathogenic/likely pathogenic CNVs and 21 patients with VUS were identified by CMA. Twenty-six pathogenic CNVs underlying well-known syndromic cases, such as Williams-Beuren syndrome, were confirmed by multiplex ligation-dependent probe amplification (MLPA). Nine novel mutations were identified by WES in thirty-fix CNV-negative ID cases. Conclusions: The study illustrated the genetic aberrations distribution of a large ID cohort in Chongqing. Compared with conventional or single methods, a tiered high-throughput diagnostic strategy was developed to greatly improve the diagnostic yields and extend the variation spectrum for idiopathic syndromic ID cases.
Highlights
Intellectual disability (ID) or developmental delay (DD) is one of the most common reasons for visiting pediatric rehabilitation or genetic counseling clinics
The results revealed that this might be a general strategy for the molecular screening of IDs
This study was performed with the approval of the Ethics Committee of Army Medical University, Chongqing, China
Summary
Intellectual disability (ID) or developmental delay (DD) is one of the most common reasons for visiting pediatric rehabilitation or genetic counseling clinics. Molecular Diagnosis of Intellectual Disability forward ID cases, ID is often accompanied by other clinical symptoms or systematic malformations, which seriously affects quality of life in this population. Genetic abnormalities are one of the most important causes of IDs (Ropers, 2008; Moeschler and Shevell, 2014; Vissers et al, 2016). Clinical phenotype analysis, and conventional auxiliary laboratory techniques, including karyotype analysis and candidate gene screening, confirm the diagnosis of IDs. there is still a large number of patients without an etiologic diagnosis. There is still a large number of patients without an etiologic diagnosis This creates a heavy burden in medical costs and social stress on the families. It is very important to illustrate the epidemiological characteristics and genetic etiology of ID in this district
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