{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:27:33Z","timestamp":1784755653250,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Child Adolesc. Psychiatry"],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To explore the genetic cause of children with unidentified etiology of neurodevelopmental disorders, thus providing references for the diagnosis, treatment and genetic counseling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and methods<\/jats:title><jats:p>Children with neurodevelopmental disorders but unidentified etiology in the Child Healthcare Department, Children's Hospital of Nanjing Medical University from November 2018 to December 2021 were retrospectively analyzed. A total of 2 ml of peripheral venous blood was collected from the child and their parents for the whole exome sequencing (WES) and copy number variation (CNV) detection. Male children were subjected to fragile X syndrome testing to determine the genetic mutations. For those with positive results, Sanger sequencing was performed to explore the mutations in the gene sites and pedigrees.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 488 (33.5%) pathogenic variations were detected among 1,457 global developmental\/intellectual disabilities (GDD\/ID) children, including 362 (24.9%) cases of monogenic mutations, and 111 (7.6%) cases of chromosomal microdeletions or microduplications. There were 15\/780 (1.92%) male children with fragile X syndrome. Single point mutations were detected in 277\/362 (76.5%) and 85\/362 (23.5%) male and female GDD\/ID children, respectively, including 295 (81.5%) cases of missense mutations, 32 (8.8%) cases of frameshift mutations, 5 (2.2%) cases of non-sense mutations and 30 (8.3%) cases of splice site mutations. In addition, there were 166 (45.8%) cases of autosomal inheritance and 196 (54.2%) cases of X-linked inheritance. The X chromosome abnormalities were mostly observed in 362 GDD\/ID children with monogenic mutations, including 15 cases of the <jats:italic>AFF2<\/jats:italic> gene mutation, 13 cases of the <jats:italic>MECP2<\/jats:italic> gene mutation and 12 cases of the <jats:italic>HUWEI<\/jats:italic> gene mutation. The <jats:italic>CREBBP<\/jats:italic> gene mutation was the most common autosome abnormality in GDD\/ID children with monogenic mutations, which was detected in five cases. There were 74 cases of chromosomal microdeletions, 31 cases of chromosomal microduplications and six cases of both. A total of 114 novel pathogenic mutations responsible for GDD\/ID were found, including four novel mutations in <jats:italic>MECP2<\/jats:italic> and <jats:italic>TRAPPC9<\/jats:italic> genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The incidence of genetic abnormalities remains high in NDD children. Abundant novel mutations are responsible for GDD\/ID in children, and can be used as references in the diagnosis of neurogenetic diseases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/frcha.2022.987339","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T05:02:55Z","timestamp":1670389375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic analysis of neurodevelopmental disorders in children"],"prefix":"10.3389","volume":"1","author":[{"given":"Dandan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"s160","DOI":"10.1590\/S0036-36342008000800009","article-title":"The WHO atlas on global resources for persons with intellectual disabilities: a right to health perspective","volume":"50","author":"Lecomte","year":"2008","journal-title":"Salud Publica Mex."},{"key":"B2","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1352\/1934-9556-54.5.342","article-title":"Outdated language: use of \u201cMental Retardation\u201d in medicaid HCBS waivers post-Rosa's Law","volume":"54","author":"Friedman","year":"2016","journal-title":"Intellect Dev Disabil."},{"key":"B3","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.annepidem.2016.01.001","article-title":"Prevalence of cerebral palsy and intellectual disability among children identified in two U.S. National Surveys, 2011-2013","volume":"26","author":"Maenner","year":"2016","journal-title":"Ann Epidemiol"},{"key":"B4","first-page":"1","article-title":"Intellectual disability in Europe: overview","author":"Beadle-Brown","year":"2003","journal-title":"Intellectual Disability in Europe. 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