Analysis of clinical features and genetic variant in a neonate with Au-Kline syndrome due to ade novo variant of theHNRNPK gene
陈珺 1戴立英 1郑洪 1刘光辉 1赵钰玮 1王娟 1许芯 杨洋
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作者信息
1. 安徽医科大学附属省儿童医院（安徽省儿童医院）新生儿科，合肥 230051
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摘要
目的 探讨1例Au-Kline综合征(AKS)新生儿的临床表型与基因特征。 方法 回顾性分析2021年1月收治入安徽医科大学附属省儿童医院的1例AKS患儿的临床资料及基因变异信息，并以"Au-Kline syndrome""Au-Kline综合症""HNRNPK""AKS"为关键词进行检索，分别检索2000年1月1日至2020年12月31日的万方数据、中国知网、PubMed数据库的相关文献，总结分析该病临床特点及遗传学特征。 结果 本例患儿为男性，临床表现为喂养困难、肌张力低下、上颚缺如至悬雍垂处及特殊面容，家系全外显子组测序检测结果提示该例患儿HNRNPK基因发生移码变异c.478dupA(p.Ile160AsnfsTer7)。Sanger测序显示该例患儿的父母未见异常，可能为新发变异。查阅数据库未见该变异有收录，根据美国医学遗传学与基因组学学会变异评级指南评级为致病性(PVS1+PS2+PM2_Supporting)。通过文献检索，纳入研究AKS患儿14例，均为HNRNPK基因新发变异，临床表现均有生长发育迟缓、运动发育迟缓及不同程度智力障碍等，具有可辨识度的特殊面容，其余高频表型为先天性心脏畸形。 结论 HNRNPK基因c.478dupA移码变异导致提前终止编码氨基酸可能是该患儿发生AKS的遗传学病因。在鉴别诊断上对于先天性多发畸形伴智力障碍亦或歌舞伎综合征患儿时，临床医师应考虑AKS的可能性。 Objective To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). Methods Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children′s Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome" , "Au-Kline syndrome" , " HNRNPK" and "AKS" . The research period was set as from January 1, 2000 to December 31, 2020. Results The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c. 478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. Conclusion The AKS in this child may be attributed to the the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.
Abstract
Objective To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). Methods Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children′s Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome" , "Au-Kline syndrome" , " HNRNPK" and "AKS" . The research period was set as from January 1, 2000 to December 31, 2020. Results The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c. 478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. Conclusion The AKS in this child may be attributed to the the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.
万方数据