論文

査読有り
2018年1月1日

Spastic paraplegia type 31: A novel REEP1 splice site donor variant and expansion of the phenotype variability

Parkinsonism and Related Disorders
  • Masaki Kamada
  • ,
  • Toshitaka Kawarai
  • ,
  • Ryosuke Miyamoto
  • ,
  • Rie Kawakita
  • ,
  • Yuki Tojima
  • ,
  • Celeste Montecchiani
  • ,
  • Laura D'Onofrio
  • ,
  • Carlo Caltagirone
  • ,
  • Antonio Orlacchio
  • ,
  • Ryuji Kaji

46
開始ページ
79
終了ページ
83
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.parkreldis.2017.10.012
出版者・発行元
Elsevier Ltd

Mutations in REEP1 have been identified in three types of neurological disorders, autosomal dominant form of Hereditary Spastic Paraplegia type 31 (SPG31), autosomal dominant distal hereditary motor neuronopathy type VB (HMN5B), and autosomal recessive form of congenital axonal neuropathy and diaphragmatic palsy. Previous studies demonstrated different molecular pathogenesis in SPG31, including loss-of-function, gain-of-function and haploinsufficiency. A four-generation family from Japan, including 12 members, was investigated clinically and genetically. Seven affected members displayed pure spastic paraplegia. Impression of genetic anticipation was observed in the family, including tendency of earlier age-at-onset and increasing severity in subsequent generations. Genetic analysis revealed a heterozygous intronic variant, c.303+2T &gt
A, in REEP1, which segregated with disease, and was also identified in one unaffected member. The variant causes exon 4 skipping leading to frame shift and a truncated transcript identified by complementary DNA sequencing of reverse transcription polymerase chain reaction products. Measurement of REEP1 transcripts in lymphocytes demonstrated a reduction through nonsense mediated mRNA decay (NMD). Our study demonstrated further evidence of allelic heterogeneity in SPG31, mutant REEP1 mRNA dosage effects through NMD and intra-familial phenotype variability.

リンク情報
DOI
https://doi.org/10.1016/j.parkreldis.2017.10.012
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29107646
ID情報
  • DOI : 10.1016/j.parkreldis.2017.10.012
  • ISSN : 1873-5126
  • ISSN : 1353-8020
  • PubMed ID : 29107646
  • SCOPUS ID : 85032279469

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