Molecular Genetics Etiology Study Of Children With General Developmental Delay/mental Retardation

Objective Study the molecular genetic etiological characteristics of global developmental delay/intellectual disability,and discuss the application value of gene detection in the diagnosis of global developmental delay/intellectual disability(GDD/ID).Methods Collect the clinical data of 230 children with global developmental delay/intellectual disability who were admitted to Neurology Department and Rehabilitation Department of Wuhan Children’s Hospital from September 2017 to December 2019.And at the same time,peripheral blood samples of children and parents were collected for gene detection and pathogenicity analysis.Results There are 230 children with GDD/ID,203 are GDD patients and 27 are ID patients,male patients are slightly more than female patients(1.57:1).In terms of comorbidity,114 patients of GDD/ID are comorbid with epilepsy,6 patients of GDD/ID are comorbid with autism spectrum disorder and 4 patients of GDD/ID are comorbid with dystonia.In 61 patients with positive copy number variant mutations,there are 52 patients with GDD,and 67 cases of CNVs mutations were detected among those patients.There are 12 cases of microdeletion and microduplication syndrome,4 cases of non-microdeletion and microduplication syndrome,benign CNV changes are found in 4 cases,likely benign CNV changes are found in 1 cases,pathogenic CNV changes are found in 17 cases,variants of uncertain significance are found in 9 cases and likely pathogenic CNVs are found in 20 cases;there are 9 patients with ID,and 11 cases of CNVs mutations are detected among ID patients,there are 6 cases of microdeletion and microduplication syndrome,1 case of non-microdeletion and microduplication syndrome,benign CNV changes are found in 1 case,pathogenic CNV changes are found in 1 case,variants of uncertain significance are found in 1 case and likely pathogenic CNVs are found in 1 case.In 169 children with positive gene mutation results,there are 151 patients with GDD,we found 103 GDD-related genes,and SCN1 A is the most common mutant gene in those children;18 patients are diagnosed with ID,and 21 genes were found to be related to ID,those genes were widely distributed in the affected patients.Among all the children with positive gene mutation results,115 GDD/ID-related genes are detected,and 38 genes are related to epileptic encephalopathy,37 genes are related to autosomal dominant intellectual disability,21 cases are linked with autosomal recessive intellectual disability and 19 genes are linked with X-linked intellectual disability.Among the patients with microdeletion and microduplication syndrome,patients with Angelman/Prader-Willi syndrome are the most.And children with de novo SCN1 A mutation make up the most part of children with epileptic encephalopathy.In female children with global developmental delay,MECP2 mutation is the most common mutant gene.Conlusions The etiology of GDD/ID is complex,genetic factors make up the most part,the affected children are often comorbid with epilepsy,autism spectrum disorder,attention deficit hyperactivity and other diseases.Timely diagnosis and differential diagnosis of this kind of children is essential in the clinic.Conducting the molecular genetic tests for the children could identify the etiology of some GDD/ID children,and it’s helpful to provide early identification,comprehensive treatment and prognosis evaluation for them.