目的 探讨1例智力发育障碍伴自闭症和语言障碍(intellectual developmental disorder with autism and speech delay,IDDAS)患儿的临床特征与基因突变情况。 方法 回顾分析1例IDDAS患儿的临床资料,应用全外显子测序对患儿及家系进行基因变异情况检测,进行致病性分析。 结果 患儿存在轻度的智力发育落后、脑损伤,并有情绪障碍、学习习惯异常及自闭倾向。相对于既往报道的IDDAS患者表型,本案例患儿存在性早熟(乳房早发育)的新表型;基因检测结果显示患儿TBR1基因存在c.874dup(p.Ser292Phefs*29)杂合移码突变,父母为野生型,即患儿的变异为新发变异。ACMG评级为致病,且此前尚未见文献报道及数据库收录,为新发现的致病性突变。 结论 TBR1基因的c.874dup(p.Ser292Phefs * 29)杂合移码突变为该患儿的致病性突变,本案例的报道丰富了IDDAS的临床表型和基因突变谱,可为后续类似患者的临床诊断提供可参考依据。 Objective To explore the clinical characteristics and gene mutations of a child with intellectual developmental disorder with autism and speech delay (IDDAS). Methods Retrospective analysis of the clinical data of a child with IDDAS, using whole exome sequencing to detect gene mutations in the patient and family, and conducting pathogenic analysis. Results The child who suffers mild mental retardation, brain damage, emotional disturbances, abnormal learning habits and autism. Compared with reported patients, the patient in this paper showed a new phenotype of puberty as praecox (Premature thelarche). Genetic tests showed that the child had a c. 874dup(p.Ser292Phefs * 29) heterozygous frameshift variant in the TBR1 gene, which was rated as pathogenic by ACMG. The proband’s parents did not have this variant, which meant the child had a de novo mutation. Furthermore, the variant had not been previously reported in the literature or included in databases, showing that this variant is a newly discovered mutation. Conclusion The c. 874dup (p.Ser292Phefs * 29) heterozygous frameshift mutation in the TBR1 gene is a candidate pathogenic mutation for this patient. The report of this case enriches the clinical phenotype and gene mutation spectrum of IDDAS, providing a reference basis for subsequent clinical diagnosis of similar patients.
A novel frameshift mutation in theTBR1 gene leads to intellectual impairment with autism in a child
Objective To explore the clinical characteristics and gene mutations of a child with intellectual developmental disorder with autism and speech delay (IDDAS). Methods Retrospective analysis of the clinical data of a child with IDDAS, using whole exome sequencing to detect gene mutations in the patient and family, and conducting pathogenic analysis. Results The child who suffers mild mental retardation, brain damage, emotional disturbances, abnormal learning habits and autism. Compared with reported patients, the patient in this paper showed a new phenotype of puberty as praecox (Premature thelarche). Genetic tests showed that the child had a c. 874dup(p.Ser292Phefs * 29) heterozygous frameshift variant in the TBR1 gene, which was rated as pathogenic by ACMG. The proband’s parents did not have this variant, which meant the child had a de novo mutation. Furthermore, the variant had not been previously reported in the literature or included in databases, showing that this variant is a newly discovered mutation. Conclusion The c. 874dup (p.Ser292Phefs * 29) heterozygous frameshift mutation in the TBR1 gene is a candidate pathogenic mutation for this patient. The report of this case enriches the clinical phenotype and gene mutation spectrum of IDDAS, providing a reference basis for subsequent clinical diagnosis of similar patients.