KMT2D基因变异所致歌舞伎综合征1例  

A case of Kabuki syndrome caused by KMT2D gene mutation

作　　者：董佳宁 张飘飘 徐芬芬 赵红洋[1] DONG Jianing;ZHANG Piaopiao;XU Fenfen;ZHAO Hongyang(Department of Pediatrics,Central Hospital Affiliated to Shandong First Medical University,Jinan 250013,Shandong,China;Shandong First Medical University/Shandong Academy of Medical Sciences,Jinan 250117,Shandong,China)

机构地区：[1]山东第一医科大学附属济南市中心医院儿科,山东济南250013 [2]山东第一医科大学山东省医学科学院,山东济南250117

出　　处：《山东大学学报（医学版）》2024年第2期90-95,共6页Journal of Shandong University:Health Sciences

基　　金：“泉城学者”建设工程(P-20230825-0025)。

摘　　要：目的 探讨歌舞伎综合征(Kabuki syndrome, KS)临床表型及基因变异类型和基因检测诊断。方法 对患儿进行外周血家系全外显子测序,并通过Sanger DNA测序验证。结果 先证者为6岁5个月的女性患儿,表现为特殊面容、发育迟缓、惊厥发作、脑电图异常、反复中耳炎病史等。患儿外周血家系全外显子测序显示,KMT2D基因(NM003482)c.3094del(p.Leu1032TrpfsTer24)存在变异。该变异为移码变异。Sanger DNA测序结果显示患儿父亲、母亲均未携带该变异,表明该变异为新发变异。根据美国医学遗传学与基因组学学会变异解读标准,该基因变异分类为PVS1+PS2+PM2,属于致病性变异。结论 患儿确诊为由KMT2D基因变异导致KS1型,为常染色体显性遗传。本研究结果表明,对于疑似KS者应做到早诊断、早干预;对于已知基因无变异的患者,应根据国际共识标准进行临床诊断,并进行随访和遗传咨询。本研究进一步丰富了KS基因变异谱,为该病的诊断和遗传咨询提供依据。Objective To explore the clinical phenotype,gene variant types and diagnosis of genetic testing of Kabuki syndrome(KS).Methods The whole exon sequencing(WES)of peripheral blood of a child was performed and verified with Sanger DNA sequencing.Results The proband was a girl aged 6 years and 5 months,who showed special facial features,developmental delay,convulsive seizures,abnormal electroencephalogram,and recurrent otitis media.WES showed KMT2D gene(NM003482)c.3094del,(p.Leu1032TrpfsTer24)mutation,which was a frameshift mutation.Sanger DNA sequencing results showed that the father and mother of the proband did not carry the KMT2D mutation,indicating that this mutation was a de novo one.According to the(American College of Medical Genetics and Genomics,ACMG)mutation interpretation standard,the mutation was classified as PVS1+PS2+PM2,which was a pathogenic mutation of KS.Conclusion The child was diagnosed with KS type 1 caused by KMT2D gene mutation,which was autosomal dominant.Our study revealed that early diagnosis and intervention should be performed for suspected KS;for patients with no known genetic variation,clinical diagnosis should be confirmed according to international consensus criteria,follow-up and genetic counseling.This study enriched the genetic mutation spectrum of KS and provided a basis for the diagnosis and genetic counseling of this disease.

关 键 词：歌舞伎综合征 KMT2D基因 特殊面容 家系基因检测 

分 类 号：R725[医药卫生—儿科]