Children with autism spectrum disorder (ASD) frequently present with co-occurring conditions that can influence autism symptom severity and complicate clinical management. However, studies with clinician-confirmed diagnoses in non-Western populations remain limited. In this multicenter cross-sectional study, 1279 children aged 3-14 years with DSM-5-confirmed ASD were recruited from eight medical centers in China. Autism symptom severity was assessed using the Childhood Autism Rating Scale (CARS). Comorbidities were identified through clinical evaluation and specialized assessments, and developmental status was measured using the Gesell Developmental Schedule (GDS) and Wechsler Intelligence Scales. Associations with CARS scores were analyzed using generalized linear regression. Of participants, 96.6% had at least one comorbidity and 71.2% had multiple comorbidities. Common conditions were intellectual developmental disorders (IDD) (87.3%), food selectivity (45.3%), insomnia disorder (16.9%), developmental regression (15.6%), and behavioral problems (14.6%). Patterns differed by sex and age: gastrointestinal problem and sleep-related interventions were more common in girls, whereas food selectivity was more common in boys. Older children showed higher rates of tic disorders, asthma, epilepsy, and offensive language, although these findings should be interpreted cautiously because the subgroup aged ≥ 6 years was small. In adjusted analyses, IDD, food selectivity, pica, insomnia disorder, and developmental regression were associated with higher CARS scores, whereas higher GDS and Wechsler scores were associated with lower CARS scores. In this Chinese cohort, comorbidities were prevalent and showed distinct sex- and age-related patterns. Several comorbidities were associated with greater autism symptom severity, underscoring the importance of comprehensive developmental and medical assessment in ASD care.

OBJECTIVE:To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. METHODS:A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children's Hospital Affiliated to Zhengzhou University in March 2023 due to "inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethic No.2022-K-L025). RESULTS:The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c.240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+PM2_Supporting+PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. CONCLUSION:The frameshift variation of TRAPPC6B gene c.240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provide basis for genetic counseling and prenatal diagnosis of this family.

Ciliary dysfunction results in multiorgan developmental diseases, collectively known as ciliopathies. The B9D1-B9D2-MKS1protein complex maintains the gatekeeper function at the ciliary transition zone (TZ). However, the function of B9 proteins and the mechanisms underlying why different variants in the same B9 gene cause different ciliopathies are not fully understood. Here, we investigated the function of B9 proteins and revealed 2 critical functions. First, the B9 complex interacted with and anchored TMEM67 to the TZ membrane. Disruption of the B9-TMEM67 complex reduced posttranslational modifications of axonemal microtubules due to deregulation of tubulin-modifying enzymes within cilia. Second, B9 proteins localized to centrioles prior to ciliogenesis, where they facilitated the initiation of ciliogenesis. In addition, we identified B9D2 variants in a cohort of patients with Joubert syndrome. We found that Joubert syndrome-associated B9D2 variants primarily affected axonemal microtubule modifications without disrupting ciliogenesis, whereas the Meckel syndrome-associated B9D2 variant disrupted both ciliogenesis and axonemal microtubule modifications. Thus, besides its role as a gatekeeper for ciliary membrane proteins, the B9 complex also controls axonemal microtubule posttranslational modifications and early stages of ciliogenesis, providing insights into the distinct pathologies arising from different variants of the same gene.

AbstractBackgroundCornelia de Lange syndrome (CdLS) is a multisystem genetic disorder, and cases caused by variants in the structural maintenance of chromosomes protein 3 (SMC3) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in SMC3 from two Chinese families.MethodsClinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio‐based whole‐exome sequencing. Pyrosequencing, chip‐based digital PCR, minigene splicing assay, and in silico analysis were carried out to elucidate the impact of novel variants.ResultsNovel heterozygous variants in SMC3 were identified in each proband. One harbored a novel splicing and mosaic variant (c.2535+1G>A) in SMC3. The mutated allele G>A conversion was approximately 23.1% by digital PCR, which indicated that 46.2% of peripheral blood cells had this variant. Additionally, in vitro minigene splicing analysis validated that the c.2535+1G>A variant led to an exon skipping in messenger RNA splicing. The other carried a heterozygous variant (c.435C>A), which was predicted to be pathogenic as well as significantly altered in local electrical potential. The former showed multiple abnormalities and marked clinical severity, and the latter mainly exhibited a speech developmental disorder and slightly facial anomalies.ConclusionBoth patients were clinically diagnosed with Cornelia de Lange syndrome 3 (CdLS3). The newly identified SMC3 gene variants can expand the understanding of CdLS3 and provide reliable evidence for genetic counseling to the affected family.

目的 观察针刺配合康复训练治疗儿童孤独症的临床疗效.方法 将86例儿童孤独症患者随机分为治疗组和对照组,每组43例.对照组采用常规康复训练治疗,治疗组在对照组基础上采用针刺治疗.观察两组治疗前后各项量表[儿童孤独症评定量表(childhood autism rating scale,CARS)、孤独症行为量表(autism behavior checklist,ABC)和婴儿-初中学生社会生活能力量表(infant-junior high school student's social living ability scale,S-M量表)]评分、语言能力各项评分(语言表达、语言理解和语言沟通)及各项生化指标[血清组织型纤溶酶原激活剂(tissue-type plasminogenactivator,t-PA)、谷胱甘肽(glutathione,GSH)水平和全血中5-羟色胺(5-hydroxytryptamine,5-HT)水平]的变化情况,并比较两组临床疗效.结果 治疗组总有效率为90.7％,明显高于对照组的76.7％(P<0.05).两组治疗后CARS评分、ABC评分、语言能力各项评分及血5-HT水平均较同组治疗前显著下降,S-M量表评分及血清t-PA、GSH水平均显著上升,差异均具有统计学意义(P<0.05).治疗组治疗后各项量表评分、语言能力各项评分及各项生化指标与对照组比较,差异均具有统计学意义(P<0.05).结论 针刺配合康复训练治疗儿童孤独症疗效确切,能改善患者语言能力,降低CARS评分、ABC评分,调节t-PA、GSH和5-HT水平.

目的 探讨不随意运动型脑瘫(DCP)患儿采用Bobath疗法对日常生活活动能力及临床疗效的影响.方法 选取2018年03月-2021年09月收治的DCP患儿共计180例,根据随机摸球法分成观察组(n=90)与对照组(n=90),对照组给予常规康复疗法,观察组给予Bobath疗法,比较两组临床疗效、日常生活活动能力、进食时间.结果 与对照组(86.67％)比较,观察组(96.67％)有着更高的治疗总有效率(P＜0.05).治疗后两组日常生活活动能力评分明显提高(P＜0.05),观察组较对照组明显更高(P＜0.05);治疗后两组GMQ、FMQ、TMQ评分均显著升高(P＜0.05),观察组 GMQ(88.26±7.65)、FMQ(89.95±9.39)和 TMQ(88.31±9.34)评分均显著高于对照组(P＜0.05).治疗后,两组喂养时间明显缩短(P＜0.05),观察组明显低于对照组(P＜0.05).结论 Bobath疗法应用于DCP患儿中,可改善日常生活活动能力,缩短进食时间,提高临床疗效.

Noonan syndrome is a common developmental disorder characterized by distinctive facial dysmorphism, short stature, congenital heart defects, pectus deformity, and developmental delay. It is related to the abnormal activation of genes involved in the RAS-MAPK signaling pathway, more than a dozen of which can be affected. However, mutations of the RRAS2 gene are rare, with only 6 different RRAS2 variants in 13 patients reported to date. In this case report, whole-exome sequencing revealed a novel heterozygous variant in the RRAS2 gene NM_012250: c.212G > A, p.(Gly71Glu). Phenotypically, our patient had typical Noonan syndrome-related clinical manifestations consistent with published reports, such as short stature, facial dysmorphism, short neck, patent foramen ovale, moderate global developmental delay, and hearing impairment. In addition, our patient also had a distal middle finger deformity and hair defect, which have not been reported in previous cases. We analyzed the clinical characteristics of all patients with Noonan syndrome caused by RRAS2 variants and reviewed the literature. This discovery expands the genetic and phenotypic spectrum of Noonan syndrome.

OBJECTIVE:To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC).METHODS:Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members.RESULTS:Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting).CONCLUSION:This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.

Objective:To observe application effects of visual and auditory integration rehabilitation training in children with global developmental delay.Methods:A prospective study was conducted on 98 children with global developmental delay admitted to the hospital from January 2019 to December 2021.They were divided into control group and study group according to the random number table method,49 cases in each group.The control group was treated with routine rehabilitation training,while the study group was treated with visual and auditory integration rehabilitation training on the basis of that of the control group.The neural developmental score,the oral motor function score,and the adaptive behavior score were compared between the two groups before and after the training.Results:After the training,the neural developmental scores of exercise,individual and society,language,hand-eye coordination and visual performance in the two groups were higher than those before the training,those in the study group were higher than those in the control group,and the differences were statistically significant(P<0.05).The scores of oral motor function such as mandibular movement,lip movement and tongue movement in the two groups were higher than those before the training,those in the study group were higher than those in the control group,and the differences were statistically significant(P<0.05).Further,the scores of independences,cognition,social self-control and other adaptive behaviors in the two groups were higher than those before the training,those in the study group were higher than those in the control group,and the differences were statistically significant(P<0.05).Conclusions:On the basis of the routine rehabilitation training,the visual and auditory integration rehabilitation training can improve the neural developmental scores,oral motor function scores and adaptive behavior scores of the children with global developmental delay.Moreover,it is superior to the routine rehabilitation training.

目的 分析前庭觉激活技术在儿童康复治疗中的应用效果和价值.方法 选取2019年3月-2022年3月住院部收治的患儿共700例,采用随机数字表法进行分组,对照组350例患儿采用常规方式进行康复治疗,观察组350例患儿在对照组基础上采用前庭觉激活技术进行康复治疗,对两组患儿治疗前后的康复效果进行比较分析.结果 观察组治疗后患儿的康复得分(97.01±0.99)分显著高于对照组的(81.04±5.05)分(P＜0.05),治疗后观察组患儿Cormer评分显著低于对照组(P＜0.05);观察组治疗后持续性错误数(13.71±2.11)、非持续性错误数(15.11±2.65)显著低于对照组(P＜0.05),WCST总应答数(71.57±9.96)、正确应答数(25.45±0.56)、完全分类数(5.24±0.24)显效多于对照组(P＜0.05);治疗后,观察组患者的QOL评分比对照组高,差异显著(P＜0.05).结论 前庭觉激活技术在儿童康复中具有较高的使用价值,有助于提高康复效果,提升患儿的行为能力与认知功能,改善患儿生活质量,临床可以选择前庭觉激活技术对患儿进行康复治疗.

OBJECTIVE:To define the nature and origin of a chromosomal aberration in a child with unexplained growth and development retardation, and to analyze its genotype-phenotype correlation.METHODS:A child who had presented at the Affiliated Children's Hospital of Zhengzhou University on July 9, 2019 was selected as the study subject. Chromosomal karyotypes of the child and her parents were determined with routine G-banding analysis. Their genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array).RESULTS:Karyotyping analysis combined with SNP array suggested that the chromosomal karyotype of the child was 46,XX,dup(7)(q34q36.3), whilst no karyotypic abnormality was found in either of her parents. SNP array has identified a de novo 20.6 Mb duplication at 7q34q36.3 [arr[hg19] 7q34q36.3(138335828_158923941)×3] in the child.CONCLUSION:The partial trisomy 7q carried by the child was rated as a de novo pathogenic variant. SNP array can clarify the nature and origin of chromosomal aberrations. Analysis of the correlation between genotype and phenotype can facilitate the clinical diagnosis and genetic counseling.

目的:观察"靳三针"头针五项疗法联合康复训练治疗儿童孤独症的临床效果.方法:80例随机分为对照组和观察组各40例.两组均用康复训练,观察组联合"靳三针"头针五项疗法.结果:观察组总有效率高于对照组(P＜0.05).两组治疗后CARS评分均降低(P＜0.05),观察组比对照组更低(P＜0.05).两组治疗后Gesell评分、PEP-3评分、PedsQLTM4.0评分均升高(P＜0.05),观察组比对照组更高(P＜0.05).结论:"靳三针"头针五项疗法联合康复训练治疗儿童孤独症疗效较好.

Objective:To explore the effect of massage combined with exercise therapy on motor function of children with cerebral palsy.Methods:Seventy-four children with cerebral palsy treated in Children's Hospital Affiliated to Zhengzhou University from June 2020 to June 2022 were selected, and were divided into an experimental group and a control group by the random number table method, with 37 cases in each group. There were 25 boys and 12 girls in the control group; they were 3-11 (6.76±1.32) years old. There were 24 boys and 13 girls in the experimental group; they were 2-10 (6.64±1.23) years old. The control group took exercise therapy, and the experimental group exercise therapy and massage. The curative effects, scores of Comprehensive Spastic Scale (CSS) and Gesell Development Quotient (DQ), motor function [Gross Motor Function Scale (GMFM) and Fine Motor Function Scale (FMFM)], and score of Balance Scale (BBS), and 10 m walking times were compared between the two groups. χ2 and t tests were applied. Results:The total effective rate of the experimental group was higher than that of the control group [94.59% (35/37) vs. 78.38% (29/37)], with a statistical difference between these two groups ( P<0.05). After the treatment, the scores of CSS, DQ, GMFM, FMFM, and BBS and 10 m walking time in the experimental group were better than those in the control group [(6.23±1.38) vs. (9.52±2.05), (90.46±3.41) vs. (82.08±3.64), (143.84±12.25) vs. (118.48±10.98), (95.03±8.44) vs. (78.58±6.67), (40.11±2.43) vs. (30.55±3.12), and (52.57±3.22) s vs. (65.18±5.19) s; all P<0.05]. Conclusion:Massage combined with exercise therapy for children with cerebral palsy can improve the curative effect and their spastic symptoms, intellectual function, motor function, balance, and walking speed.

目的:观察多参数生物反馈治疗(MPB)对孤独症谱系障碍(ASD)儿童注意力障碍及多动行为的影响。方法:采用随机数字表法将50例ASD患儿分为观察组及对照组，每组25例。2组患儿均给予个体化常规康复训练，包括语言认知训练、社交沟通训练、感觉统合训练等，观察组患儿在此基础上辅以MPB治疗。2组患儿均每天治疗1次，每周治疗5 d，连续治疗4周为1个疗程。于治疗前、治疗2个疗程后分别采用SNAP-IV评定量表(家长版)、整合视听连续执行测试(IVA-CPT)对2组患儿进行疗效评定。结果:治疗后2组患儿SNAP-IV、IVA-CPT各项因子评分均较入选时明显改善( P<0.05)；并且观察组患儿上述指标评分亦显著优于对照组水平( P<0.05)。 结论:在常规干预基础上辅以MPB治疗能有效改善ASD患儿注意力障碍，并纠正其多动行为，从而减轻疾病严重程度。

目的 探讨学龄前孤独症谱系障碍(ASD)儿童的患病危险因素.方法 选取 2020 年 7 月至 2022 年 4 月在郑州大学附属儿童医院就诊的 87 例 3～6 岁ASD儿童为研究对象并设为观察组,对照组为 80 例 3～6 岁同时期在本院进行体检的正常儿童.对两组研究对象进行问卷调查表、ABC量表、CARS量表及S-S语言发育迟缓量表,分析ASD儿童的患病危险因素.结果 观察组患儿ABC、CARS评分均显著高于对照组,差异有统计学意义(P＜0.05).观察组中,男、女性ASD患病率分别为 82.76%、17.24%,差异有统计学意义(P＜0.05).单因素统计分析表明,患儿性别、喂养方式、母亲怀孕年龄、父亲性格、母亲性格、父母关系资料,差异有统计学意义(P＜0.05),是ASD儿童患病的的影响因素.由Logistic回归分析发现,患儿男性性别、父亲性格内向、母亲怀孕年龄偏大是ASD儿童患病的独立危险因素.87 例ASD儿童中有 81 例存在语言发育迟缓,发生率为 93.10%.结论 ASD的患病因素包括:男性、父亲性格内向、母亲怀孕年龄偏大,且ASD儿童多存在语言发育迟缓的现象,减少相关危险因素,及早发现并治疗,可降低ASD的发病率.

目的:观察情景互动训练联合常规康复训练在运动障碍患儿中的应用效果.方法:选取 2020 年 3 月至 2022 年 1 月该院收治的 88 例运动障碍患儿进行前瞻性研究,依据随机数字表法将其分为研究组与对照组各 44 例.对照组采取常规康复训练,研究组在对照组基础上联合情景互动训练,比较两组训练前后粗大运动功能[粗大运动功能评估量表(GMFM-88)]评分、足背屈角、三维步态情况,胫前肌和腓肠肌肌电值,躯干功能[中文版躯干损伤量表(TIS)]评分和平衡功能[Berg平衡量表(BBS)]评分.结果:训练后,两组D区、E区等GMFM-88、BBS和TIS评分均高于训练前,且研究组高于对照组,两组足背屈角、摆动相、步长、步速均大于训练前,且研究组大于对照组,两组支撑相、胫前肌和腓肠肌肌电值均低于训练前,且研究组低于对照组,差异有统计学意义(P＜0.05).结论:情景互动训练联合常规康复训练应用于运动障碍患儿可提高GMFM-88、BBS、TIS评分和足背屈角,改善三维步态情况,降低胫前肌和腓肠肌肌电值,效果优于单纯常规康复训练.

OBJECTIVE:To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS).METHODS:A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed.RESULTS:The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting).CONCLUSION:The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.

Background: Kinase D-interacting substrate of 220 kDa (KIDINS220) is a multifunctional scaffolding protein essential for neuronal development. It has been implicated in neurological diseases with either autosomal dominant (AD) or autosomal recessive (AR) inheritance patterns. The molecular mechanisms underlying the AR/AD dual nature of KIDINS220 remain elusive, posing challenges to genetic interpretation and clinical interventions. Moreover, increased KIDINS220 exhibited neurotoxicity, but its role in neurodevelopment remains unclear.Objective: The aim was to investigate the genotype-phenotype correlations of KIDINS220 and elucidate its pathophysiological role in neuronal development.Methods: Whole-exome sequencing was performed in a four-generation family with cerebral palsy. CRISPR/Cas9 was used to generate KIDINS220 mutant cell lines. In utero electroporation was employed to investigate the effect of KIDINS220 variants on neurogenesis in vivo.Results: We identified in KIDINS220 a pathogenic nonsense variant (c.4177C > T, p.Q1393*) that associated with AD cerebral palsy. We demonstrated that the nonsense variants located in the terminal exon of KIDINS220 are gain-of-function (GoF) variants, which enable the mRNA to escape nonsense-mediated decay and produce a truncated yet functional KIDINS220 protein. The truncated protein exhibited significant resistance to calpain and consequently accumulated within cells, resulting in the hyperactivation of Rac1 and defects in neuronal development.Conclusions: Our findings demonstrate that the location of variants within KIDINS220 plays a crucial role in determining inheritance patterns and corresponding clinical outcomes. The proposed interaction between Rac1 and KIDINS220 provides new insights into the pathogenesis of cerebral palsy, implying potential therapeutic perspectives. (c) 2023 International Parkinson and Movement Disorder Society.

脑性瘫痪是以运动障碍、姿势异常、肌力和肌张力改变为表现的一组综合征.前庭系统的主要功能为维持头部及躯干稳定,保持身体平衡及动作协调,脑瘫患儿的前庭功能损害会导致平衡功能受损、姿势控制不良、眼球运动困难、头眼协调能力差及运动发育延迟等.前庭康复训练是一种个体化的非药物性的康复治疗项目,其主要通过前庭适应、前庭习服、前庭代偿等机制,通过反复强化前庭感受器,提高神经细胞兴奋性,促进损伤的脑组织区域产生新的神经通路,从而有效改善患者的运动功能、姿势控制、平衡能力、肌力和肌张力、眼球运动等.目前,前庭康复训练在成人中已被广泛应用于帕金森、脑卒中、脊髓损伤、阿尔茨海默病等患者,在儿童中也被应用于孤独症谱系障碍、注意力缺陷多动障碍、全面发育迟缓等患儿,对脑性瘫痪患儿影响的研究报道较少.基于上述背景,文章对前庭康复训练机制以及国内外有关前庭康复训练对脑性瘫痪患儿治疗的研究进展情况进行总结,以期为更好地改善脑性瘫痪患儿生活质量提供帮助.

AbstractBackground Developmental delay (DD) and intellectual disability (ID) represent one of the biggest medical and social challenges in our society with a prevalence of 1 ~ 3% worldwide. Currently, at least 50% of DD/ID cases remained unexplained. Mental retardation, autosomal dominant 21 (MRD21), caused by mutations inCTCF, is a rare DD/ID-related disease. The clinical phenotypes of MRD21 are highly variable but are not considered sufficiently distinct to be clinically recognizable. To date, only 37 pathogenic/likely pathogenic mutations inCTCFassociated with MRD21 have been identified, and the pathogenesis ofCTCFremains largely unknown. Methods Whole exon sequencing (WES) and bioinformatics analysis were used to identify the mutation as being responsible for an 18-month-old girl with unexplained DD, abnormality of the face and congenital heart disease. The origin of the mutation was analyzed by Sanger sequencing. The pathogenicity of the missense mutation was mainly analyzed by western blot (WB) and molecular dynamics (MD) simulations. Results We identified a novel missense mutation inCTCF(c.1115C > T, p. Ser372Phe) using WES, and Sanger sequencing indicated that the mutation wasde novo. The expression levels of CTCF in 293T cells were unaltered by the missense mutation. However, MD simulations supported the pathogenicity of the p. Ser372Phe mutation, which resulted a decrease in the binding affinity of CTCF with DNA. Conclusions Our study broadens the mutational spectrum ofCTCFand provides a better understanding of the pathogenicity of missense mutations inCTCF. This is the first time that MD simulations have been applied to evaluate the pathogenicity of missense mutations inCTCF.