1例经典型Hallervorden-Spatz综合征的临床特征及基因分析  

Clinical characteristics and gene analysis of a case of classical Hallervorden-Spatz syndrome

作　　者：汪小霞 余维莎 于飞[1] 张宁[1] WANG Xiaoxia;YU Weisha;YU Fei;ZHANG Ning(Department of Endocrinology,Genetics and Metabolism of Children,Hubei Maternal and Child Health Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430000,China)

机构地区：[1]华中科技大学同济医学院附属湖北妇幼保健院儿童内分泌遗传代谢科,湖北武汉430000

出　　处：《中国优生与遗传杂志》2023年第6期1262-1265,共4页Chinese Journal of Birth Health & Heredity

摘　　要：目的探讨1例Hallervorden-Spatz综合征(HSS)患儿的临床表型、影像学改变及基因型特点,提高临床医生对该病认识。方法回顾性分析1例因“发育迟滞、发作性肢体扭曲”就诊,经基因检测确诊为PANK2基因突变所致的经典型HSS患儿,通过与中国人群独立的内部变异数据库和公共变异数据库进行比较,并行文献综述,发现且验证了候选变异的次等位基因频率(MAF)特征。结果患儿为5岁11月大男童,有“脑瘫”病史,因病情进展出现发作性肌紧张、肢体扭曲,复查头颅MRI显示“虎眼征”,双侧苍白球区对称性病变,全外显子测序发现PANK2基因复合杂合突变:NM_153638.3:D452G和E149*,这2个突变位点仅在中国患者中报道,公共数据库显示也只在东亚人群中有分布,MAF分别为0.011%(2/18394,gnomAD东亚)和0.099%(1/1008,1000Genomes东亚),并在中国人群内部数据库中得到了验证(分别为0.016%和0.100%,智因东方)。结论通过加入中国人群基因变异数据库分析,有助于发现国人特有的致病性变异热点,这对了解中国患者罕见疾病的分子遗传学特征有重要意义。Objective To investigate the clinical phenotype,radiological changes and genotype characteristics in a patient diagnosed with Hallervorden-Spatz syndrome(HSS),and to improve the understanding of the disease.Methods Retrospective study was performed in a child who presented with“developmental delay and episodic limb distortion”and was diagnosed with classical HSS by detecting pathogenic variants in the PANK2 gene.In comparison to an independent in-house variants database of Chinese population and public variant databases,followed by the literature review,the minor allele frequency(MAF)characteristics of the candidate variants were found and verified.Results The patient,5 years and 11 months old boy,had a history of“cerebral palsy”,because of progressive episodic hypertonia and limb distortion,he was sent for re-examination and his cranial MRI showed“eye of the tiger sign”,symmetry lesions in the bilateral globus pallidus area.Whole-exome sequencing found compound heterozygous variants,NM_153638.3:D452G and E149*,in PANK2.Both variants were reported only in Chinese patients and public databases showed that the variants were exclusively detected in East Asian populations with MAF of 0.011%(2/18394,gnomAD East Asia)and 0.099%(1/1008,1000 Genomes East Asia),respectively,which were verified in the in-house database of Chinese population(0.016% and 0.100%,respectively,Chigene).Conclusion An extra Chinese in-house variant database facilitates finding recurrent mutations in local population,which is critical for understanding the genetic characteristics of rare diseases in Chinese patients.

关 键 词：HALLERVORDEN-SPATZ综合征 PANK2基因 虎眼征 次等位基因频率 中国人 

分 类 号：R725.9[医药卫生—儿科]