It is hard to make an early and accurate diagnosis of developmental delay (DD) /mental retardation (MR) in children due to complex etiology, diverse and heterogeneous clinical manifestations of the disease. There are few large-sample analyses of the clinical and genetic test data of these children in China.

To perform an analysis of genetic test results of children with DD/MR, providing evidence for genetic diagnosis, treatment plan formulation and prognosis assessment in such children.

Ninety-three children with DD/MR of unknown origin were selected from Department of Rehabilitation, Kunming Children's Hospital from September 2017 to September 2021. Whole-exome sequencing (WES) was performed to explore pathogenic gene mutations associated with clinical manifestations. Copy number variation (CNV) detection was conducted to examine the characteristics of pathogenic CNVs. The detection of gene mutations was analyzed.

The DD/MR in the children was mainly manifested by motor or global DD, or MR, and with a developmental level falling behind normal developmental milestones. Seventy-four cases (79.6%) were detected with genetic variants, and the detection rate was 79.6%, among whom 40 (43.0%) with pathogenic gene mutations, 13 (14.0%) with gene CNVs, and 21 (22.6%) with mutations of uncertain significance. The genetic test results involved more than 50 pathogenic genes in total. The most prevalent disease caused by gene mutation was spinal muscular atrophy caused by mutations in the SMN1 gene (10.0%, 4/40), followed by Bethlem myopathy-1 caused by mutations in the COL6A2 gene (7.5%, 3/40) and Joubert syndrome-21 caused by mutations in CSPP1 (5.0%, 2/40) .

Pathative gene mutations and gene copy number variants may be main causes of DD/MR. SMN1, COL6A2, and CSPP1 are common mutated genes in DD/MR patients. WES combined with CNV detection may greatly contribute to the exploration of the etiology of DD/MR, especially for DD/MR manifested by atypical phenotypes and clinical manifestations.

发育迟缓（DD）/精神发育迟缓（MR）病因复杂，临床表现多样、异质性强，该类患儿的早期精准诊断十分困难，目前国内鲜有大样本分析该类患儿的临床资料及基因检测结果。

分析DD/MR患儿基因检测结果，为DD/MR患儿确定遗传学诊断、制订治疗方案和判断预后提供依据。

选取2017年9月至2021年9月于昆明市儿童医院康复科就诊的致病原因尚不明确的93例DD/MR患儿为研究对象，对患儿进行全外显子组测序（WES）和拷贝数变异（CNV）检测，分析与患儿临床表现相关的致病性基因突变位点和CNV特点，分析基因突变检出情况。

93例患儿临床表现包括运动发育落后、智力低下或全面性发育落后，发育水平落后于正常发育里程碑。共检出遗传变异74例，检出率为79.6%，其中40例（43.0%）为致病性基因突变，13例（14.0%）为基因CNV，21例（22.6%）为突变意义未明。基因检测结果共涉及50种基因，所致疾病中SMN1基因突变引起的脊髓性肌萎缩症所占比例最高（10.0%，4/40），其次为COL6A2基因突变引起的Bethlem综合征1型（7.5%，3/40）及CSPP1基因突变所致的Joubert综合征21型（5.0%，2/40）。

致病基因突变和基因CNV可能是导致DD/MR的主要病因，SMN1、COL6A2、CSPP1为DD/MR患者常见突变基因，WES结合CNV检测对明确DD/MR的病因，特别是对诊断表型和临床表现不典型的患儿有重要意义。