title: Mutational spectrum of the SPAST and ATL1 genes in Korean patients with hereditary spastic paraplegia.
abstract: Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of diseases characterized by insidiously progressive lower-extremity weakness and spasticity. Spastic paraplegia 4 (SPAST) is the most common type of uncomplicated autosomal dominant HSP (40% of such cases), and spastic paraplegia 3A (ATL1) is the second most common. Here, we conducted mutational analysis of the SPAST and/or ATL1 genes in 206 unrelated patients with HSP. DNA sequencing and multiplex ligation-dependent probe amplification was used to analyze SPAST or ATL1 pathogenic variants. To confirm splice-site pathogenic variants, mRNA transcripts were analyzed by reverse transcription-polymerase chain reactions and sequencing. Among the 52 patients with medical records and SPAST or ATL1 gene pathogenic variants or novel unclassified variants, 50 showed spasticity or weakness in their lower extremities. We identified 16 known and 18 novel SPAST pathogenic variants and 2 known and a novel splicing pathogenic variants in ATL1. We also identified 4 unclassified SPAST variants in 5 patients and an unclassified ATL1 variant in 1 patient. Further, a novel leaky-splicing variant (c.1537-11A>G) was found in SPAST, which caused skipping of exon 13 or exons 13-14. Among the 206 unrelated patients with HSP, SPAST or ATL1 pathogenic variants and potentially pathogenic variants were identified in 52 patients, a low pathogenic variant rate compared to previous results. Results from our study suggest that other genes may be involved in HSP in the Korean population.
authors.affiliation: Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsangnam-do, South Korea.
authors.forename: Hyunwoong
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University Medical School, Gwang-Ju, South Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Green Cross Reference Laboratory, Yong-In, Gyeonggi-do, South Korea.
authors.forename: Seungman
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, National Medical Center, Seoul, South Korea.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jung Ae
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Sung Im
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Kwang-Woo
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: mwseong@snu.ac.kr.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D000074181:Spastin; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human
keywords: ATL1; Gene; Hereditary spastic paraplegia; Pathogenic variants; SPAST; Sequencing