Kabuki综合征2例临床表型和基因变异分析

The clinical phenotype and gene variation of two children with Kabuki syndrome

目的分析Kabuki综合征(KS)的临床和分子遗传学特征。方法回顾分析2例以生长迟缓就诊的KS患儿的临床资料,并对患儿及其父母进行矮小相关基因组或全外显子组测序及全基因组拷贝数变异(CNV)检测。结果2例女性患儿,均因喂养困难、生长迟缓就诊;临床表现均为特殊容貌,按年龄身长、按年龄体质量的Z评分均<-2.5,发育迟缓,脊椎侧弯,头颅磁共振成像异常。例1伴右肾异位,例2伴房间隔缺损。基因检测发现,例1患儿KMT2D基因34号外显子c.10139delA(p.K3380Sfs*12)杂合变异;例2患儿KDM6A基因16号外显子c.1909-1912delTCTA(p.Ser637Thrfs*53)杂合变异,均为移码变异,新发、致病性变异。结论生长迟缓、喂养困难伴发育迟缓及特殊面容的患儿可行遗传学诊断。

Objective The clinical and molecular genetic characteristics of Kabuki syndrome(KS).Methods The clinical data of 2 children with KS who were treated with growth retardation was analyzed etrospectively.Using the nextgeneration sequencing technology,the children and their parents were sequenced with short stature-related genome or whole exome and whole genome copy number variation(CNV)detection.Results Two female children aged 36 months and 3 months old went to the doctor due to feeding difficulties and growth retardation.The clinical manifestations are special appearance,the length and weight Z scores for age are less than-2.5,developmental delay,scoliosis,and abnormal head MRI.Case 1 has an ectopic right kidney,and case 2 has atrial septal defect.The results of genetic testing and analysis show KMT2D gene exon 34 c.10139 delA(p.K 3380 Sfs*12)heterozygous mutation.KDM6A gene exon 16 c.1909-1912 delTCTA(p.Ser 637 Thrfs*53)heterozygous mutation.All are frameshift mutations.They are new and pathogenic mutations.Conclusions It is suggesting that children with growth retardation,feeding difficulties with growth retardation and special facial features should undergo genetic examination as soon as possible to confirm the diagnosis.