title: Whole-genome sequencing of two probands with hereditary spastic paraplegia reveals novel splice-donor region variant and known pathogenic variant inSPG11.
abstract: Hereditary spastic paraplegias (HSPs) are a group of heterogeneous neurodegenerative disorders, which are often presented with overlapping phenotypes such as progressive paraparesis and spasticity. To assist the diagnosis of HSP subtypes, next-generation sequencing is often used to provide supporting evidence. In this study, we report the case of two probands from the same family with HSP symptoms, including bilateral lower limb weakness, unsteady gait, cognitive decline, dysarthria, and slurring of speech since the age of 14. Subsequent whole-genome sequencing revealed that the patients are compound heterozygous for variants in theSPG11gene, including the paternally inherited c.6856C>T (p.Arg2286*) variant and the novel maternally inherited c.2316+5G>A splice-donor region variant. Variants inSPG11are the common cause of autosomal recessive spastic paraplegia type 11. According to the ClinVar database, there are already 101 reported pathogenic variants inSPG11that are associated with HSPs. To our knowledge, this is the first report ofSPG11variants in our local population. The novel splice variant identified in this study enriches the catalog ofSPG11variants, potentially leading to better genetic diagnosis of HSPs.
authors.affiliation: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR;; Partner State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR.
authors.forename: Allen Chi-Shing
authors.identifier: 0000-0002-9568-8316
authors.initials: AC
authors.lastname: Yu
authors.affiliation: Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR.
authors.forename: Anne Yin-Yan
authors.initials: AY
authors.lastname: Chan
authors.affiliation: Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR;; Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR.
authors.forename: Wing Chi
authors.initials: WC
authors.lastname: Au
authors.affiliation: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR;; Partner State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR;; Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR.
authors.forename: Ting Fung
authors.initials: TF
authors.lastname: Chan
authors.affiliation: School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR;; Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR.
authors.forename: Ho-Yin Edwin
authors.identifier: 0000-0003-4307-474X
authors.initials: HE
authors.lastname: Chan
mesh_terms: D000328:Adult; D001483:Base Sequence / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010264:Paraplegia / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000378:metabolism; D000073336:Whole Genome Sequencing / Q000379:methods
chemical_list: D011506:Proteins; D022821:RNA Splice Sites; C520412:SPG11 protein, human
keywords: gait imbalance; slowed slurred speech; spastic dysarthria; spastic gait; spastic paraparesis; spastic paraplegia