染色体6pter-p24缺失患者的临床表型及遗传学分析

Clinical phenotype and genetic analysis of patients with chromosome 6pter-p24 deletion

目的 探讨染色体6pter-p24缺失患者的临床表型及遗传学分析。方法 收集患者临床表型及实验室检查结果,应用常规G显带核型分析患儿及父母外周血染色体核型,用SNP-array技术对患儿进行染色体CNVs分析,qPCR验证拷贝数异常区域的真实性及其变异来源,并检索相关文献进行总结分析。结果 患儿主要临床表现为面容异常、短颈、角膜混浊、听力受损、先天性心脏病、先天性肛门闭锁并直肠舟状窝瘘和手指畸形等。染色体核型结果提示6pter-p24存在缺失;SNP-array检测提示6p25.3p24.2(156,974_11,424,578)存在11.2 Mb杂合缺失。用检索词“6p25缺失综合征”“6p24缺失综合征”“6p25 deletion syndrome”和“6p24 deletion syndrome”检索中英文数据库,共检索到涉及6pter-p24缺失的相关文献共12例患者,比较发现这些患者的临床表现相似,但本病例患儿先天性肛门闭锁并直肠舟状窝瘘表型在其他病例中未见报道。结论 6p25.3p24.2(156,974_11,424,578)的新发杂合缺失变异是患儿的发病原因。染色体6p24缺失综合征表型复杂多样,易被漏诊,综合应用遗传学检测技术可帮助罕见病患儿精准诊断,为优生优育提供科学依据。

Objective To explore the clinical features and genetic characteristics patients with 6pter-p24 deletion syndrome.Methods Clinical phenotype and laboratory test results of patients were collected.Conventional peripheral blood karyotypes of the child and his parents were analyzed with G-banding.SNP-array was used to determine CNVs analysis.Candidate CNVs and its origin were verified by qPCR,and relevant literatures were summarized and analyzed.Relevant literatures were summarized and analyzed.Results The child presented with dysmorphic facial features,short neck,corneal clouding,hearing loss,congenital heart defects,congenital anal atresia and rectal navicular fistula and finger deformity.Chromosomal analysis revealed that the child had a deletion of 6pter-p24.SNP-array indicated that the child had carried a heterozygous deletion of 11.2 Mb on 6p25.3 p24.2.The Chinese and English databases were searched with the search terms“6p25缺失综合征”,“6p24缺失综合征”,“6p25 deletion syndrome”and“6p24 deletion syndrome”.A total of 12 patients with 6pter-p24 deletion were found in literatures.Comparison showed that the clinical manifestations of these patients were similar,but the phenotype of congenital anal atresia and rectal navicular fistula in this case was not reported in other cases.Conclusion The de novo 6p25.3p24.2(156,974_11,424,578)deletion was identified.The phenotype of chromosome 6p24 deletion syndrome is complex and diverse,which is easy to be missed.The comprehensive application of genetic detection technology can help the accurate diagnosis of children with rare diseases,and provide scientific basis for eugenics and childbearing.