遗传性痉挛性截瘫5A型一个家系的临床表型及遗传学分析

Clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A

目的探讨1个遗传性痉挛性截瘫5A型(SPG5A)家系的临床表型及遗传学特点。方法选取2022年8月15日在河南省儿童医院疑诊为遗传性痉挛性截瘫(HSP)的1个家系作为研究对象。收集该家系的临床资料,采集家系成员的外周血样,提取基因组DNA,进行家系全基因组测序(trio-WGS),对可疑致病性变异进行Sanger测序验证。结果该家系患儿为1岁男性,主要表现为小头畸形,颜面部、四肢远端及躯干背侧多毛,智力和运动发育落后,双下肢肌张力高,双侧膝腱反射亢进,病理征阳性;其父母及姐姐表型均未见明显异常。Trio-WGS检测发现患儿携带CYP7B1基因c.1250G>A(p.Arg417His)纯合变异,其母亲携带杂合变异,父亲和姐姐均为野生型,变异来源分析为8号染色体(chr8)母源单亲二倍体(UPD),Sanger测序与trio-WGS结果一致。既往未见chr8母源UPD导致SPG5A的报道。结论上述SPG5A患儿为复杂型HSP,chr8 CYP7B1基因c.1250G>A母源UPD可能是其遗传学病因。

Objective To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A(SPG5A).Methods A pedigree suspected for Hereditary spastic paraplegia(HSP)at Henan Children′s Hospital on August 152022 was selected as the study subject.Clinical data of the pedigree was collected.Peripheral blood samples were collected from members of the pedigree.Following extraction of genomic DNA,trio-WGS was carried out,and candidate variant was verified by Sanger sequencing.Results The child,a 1-year-old boy,had presented with microcephaly,hairy face and dorsal side of distal extremities and trunk,intellectual and motor development delay,increased muscle tone of lower limbs,hyperreflexes of bilateral knee tendons,and positive pathological signs.His parents and sister both had normal phenotypes.Trio-WGS revealed that the child has harbored a homozygous c.1250G>A(p.Arg417His)variant of the CYP7B1 gene,for which his mother was heterozygous,the father and sister were of the wild type.The variant was determined to have originated from maternal uniparental disomy(UPD).The result of Sanger sequencing was in keeping with the that of trio-WGS.SPG5A due to maternal UPD of chromosome 8 was unreported previously.Conclusion The child was diagnosed with SPG5A,a complex type of HSP,for which the homozygous c.1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.