Different patterns of HSP in Korea

Posted - September 2015 in Research Highlights

Other genes may be involved

 

This study of HSP in South Korea found just 25% of HSP cases were SPG4 (SPAST) and SPG3A (ATL1) combined. Many other studies across a large number of ethnic groups have consistently found the combined tally of these 2 most common forms of HSP around double this figure.

 

The study of 206 unrelated HSPers also discovered 18 new SPAST mutations and one new ATL1 mutation.

 

The results suggest that other genes may be involved in HSP in the Korean population.

 

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.

 

SOURCE: J Neurol Sci. 2015 Jul 17. pii: S0022-510X(15)00445-1. doi: 10.1016/j.jns.2015.07.024. [Epub ahead of print] Copyright © 2015. Published by Elsevier B.V. PMID: 26208798 [PubMed – as supplied by publisher]

 

Mutational spectrum of the SPAST and ATL1 genes in Korean patients with hereditary spastic paraplegia.

 

Park H1, Kang SH2, Park S3, Kim SY4, Seo SH5, Lee SJ5, Lee JA5, Cho SI5, Sung JJ6, Lee KW6, Kim JY7, Park SS8, Seong MW9.

  • 1Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsangnam-do, South Korea.
  • 2Department of Laboratory Medicine, College of Medicine, Chosun University Medical School, Gwang-Ju, South Korea.
  • 3Green Cross Reference Laboratory, Yong-In, Gyeonggi-do, South Korea.
  • 4Department of Laboratory Medicine, National Medical Center, Seoul, South Korea.
  • 5Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
  • 6Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
  • 7Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
  • 8Department 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.
  • 9Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: [email protected]

 

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