目的对3个遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP)患者家系的临床表现及致病基因进行分析。方法对甘肃省妇幼保健院(甘肃省中心医院)收集的3个HSP患者家系进行基因分析。结果家系1中先证者为FA2H c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)纯合变异导致的常染色体隐性痉挛性截瘫35型,家系2中的先证者为AP4B1 c.1399G>T(p.Glu467Ter)纯合变异导致的常染色体隐性痉挛性截瘫47型,家系3中先证者为SPG11 c.7023C>G(p.Tyr2341Ter)的纯合变异导致的常染色体隐性痉挛性截瘫11型。其中,AP4B1 c.1399G>T(p.Glu467Ter)位点为尚未报告的变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)指南,该变异的致病性评级为致病性变异。结论本研究丰富了HSP致病基因AP4B1的变异谱,为提高临床对HSP患者的认识与诊断能力提供了基础性数据。
报道一例以共济失调、全身震颤、眼肌麻痹、痉挛性截瘫为临床表现的成人起病的常染色体隐性遗传的复杂型遗传性痉挛性截瘫(hereditary spastic paraplegias, HSP)。患者通过全外显子基因测序,找到DDHD2基因[c.335G>A, p.R112Q]的纯合突变,提示该突变可能与该患者的临床表现相关。本例报告为复杂型HSP的遗传基础提供了新的见解,并强调了基因检测在此类罕见疾病诊断中的重要性。We report a case of adult-onset autosomal recessive complex hereditary spastic paraplegia (HSP), characterized by a combination of ataxia, generalized tremor, ophthalmoplegia, and spastic paraplegia. Genetic analysis through whole-exome sequencing identified a homozygous mutation in the DDHD2 gene (c.335G>A, p.R112Q), which is likely responsible for the observed clinical manifestations. This case report provides new insights into the genetic basis of complex HSP and highlights the importance of genetic testing in the diagnosis of such rare diseases.
