RLIM基因突变致Tonne-Kalscheuer综合征的临床特点和遗传学分析

Clinical characteristics and genetic analysis of Tonne-Kalscheuer syndrome caused by a novel RLIM mutation

目的探讨RLIM基因突变所致Tonne-Kalscheuer综合征(TOKAS)的临床表型及遗传学特征。方法回顾分析2023年12月于重庆市红十字会医院(江北区人民医院)诊治的1例以发育落后、隐睾为主诉的TOKAS患儿为研究对象。采集这名患儿包括检查数据在内的临床资料,对患儿及其生物学父母行全医学外显子测序,并通过文献检索,归纳总结国内外已报道的RLIM基因突变所致TOKAS病例的临床特点以及遗传学特征。结果患儿男,5岁,临床以运动发育落后、特殊外貌为特征。全外显子组测序结果提示其携带RLIM基因c.1123G>A位点突变,现国内尚未见以该位点突变致使TOKAS的文献报道。与4篇国外文献报道的42例RLIM基因突变致病患者一同进行总结,发现共存在10种不同的基因突变,男性患儿主要临床特征表现为包括整体运动言语发育迟缓(占比100%),智力障碍(占比100%),言语攻击(占比100%)、发脾气或暴怒(占比100%)、焦虑(占比93.3%)、重复的自闭症或强迫症行为(占比88.2%)和多动症(占比83.3%)。结论RLIM基因c.1123G>A(p.Val375Met)是该患儿的病因。本研究丰富了国内RLIM相关的TOKAS基因突变报道,并为产前诊断分析、临床诊断提供了依据。

Objective To explore the clinical phenotypes and genetic characteristics of Tonne-Kalscheuer syndrome(TOKAS)caused by a novel RLIM mutations.Methods A case of TOKAS children diagnosed and treated at Chongqing Red Cross Hospital(JiangBei People's Hospital)in December of 2023 with main complaints of developmental delay was retrospectively analyzed.The clinical material including examination data of the child were collected,comprehensive medical exome sequencing was performed on the child and his biological parents,and the clinical characteristics and genetic characteristics of TOKAS cases caused by RLIM mutations reported at home and abroad were summarized.This study summarizes the reported clinical characteristics of TOKAS caused by RLIM mutations.Results The male patient,aged 5 years old,was clinically characterized by delayed motor development and special appearance.The results of comprehensive medical exome sequencing indicate that he carries the c.1123G>A frameshift mutation in RLIM.There are no domestic reports that this site mutation causes TOKAS.Compared with the 42 cases of patients with RLIM variants reported in 4 foreign literatures,there are 10 different gene variants.The main clinical characteristics of male children include overall motor and speech development delay(accounting for 100%),intellectual disability(accounting for 100%),verbal aggression(accounting for 100%),tantrums or angry outbursts(accounting for 100%),anxiety(accounting for 93.3%),repetitive autistic or obsessive-compulsive behavior(accounting for 88.2%)and ADHD(accounting for 83.3%).Conclusion RLIM gene c.1123G>A(p.Val375Met)is the cause of this child.This study enriches domestic reports of TOKAS frameshift variat related to RLIM and provides a basis for prenatal diagnostic analysis and clinical diagnosis.