CHRNG基因新发变异致多发性翼状胬肉综合征1例的遗传学分析

Analysis of a case of Multiple pterygium syndrome due to a novel variant of CHRNG gene

目的探讨1例多发性翼状胬肉综合征(MPS)患儿的临床特征及遗传学病因。方法选取2020年8月19日于广州市妇女儿童医疗中心骨科就诊的1例MPS患儿作为研究对象。收集患儿的临床资料,采集患儿及其父母的外周血样,对患儿进行全外显子组测序(WES),用Sanger测序对候选变异进行家系验证,并进行生物信息学分析。结果患儿为女性,11岁,因"发现脊柱侧弯8年,加重伴双肩不等高1年"就诊。WES检测结果提示其携带CHRNG基因c.55+1G>C纯合剪接变异,Sanger测序证实其父母均携带CHRNG基因c.55+1G>C杂合剪接变异。生物信息学分析:CHRNG基因c.55+1G>C变异在CNKI、万方数据知识服务平台及HGMG等数据库中均未见收录。经Multain在线软件分析,该位点所编码的氨基酸在不同物种中高度保守。经CRYP-SKIP在线软件预测,该变异导致第1外显子潜在剪接位点激活与跳跃的概率分别为0.30与0.70。确诊患儿罹患MPS。结论CHRNG基因c.55+1G>C变异可能是本研究MPS患儿的遗传学病因。

Objective To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome(MPS).Methods A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children′s Medical Center Affiliated to Guangzhou Medical University on August 19,2020 was selected as the study subject.Clinical data of the child was collected.Peripheral blood samples of the child and her parents were also collected.Whole exome sequencing(WES)was carried out for the child.Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis.Results The child,an 11-year-old female,had a complain of"scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year".WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene,for which both of her parents were heterozygous carriers.By bioinformatic analysis,the c.55+1G>C variant has not been recorded by the CNKI,Wanfang data knowledge service platform and HGMG databases.Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species.As predicted with the CRYP-SKIP online software,the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70,respectively.The child was diagnosed with MPS.Conclusion The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.