High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia

Min Yu Lan, Yung Yee Chang, Tu Hseuh Yeh, Szu Chia Lai, Chia Wei Liou, Hung Chou Kuo, Yih Ru Wu, Rong Kuo Lyu, Jen Wen Hung, Ying Chao Chang, Chin Song Lu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs. Methods: A total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed. Results: Mutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20 ± 18 years) compared with those with preservation of partial or total AAA cassette (32 ± 19 years, p = 0.041). For those with SPG4 mutations, disease severity was related to the patients' current age, and the progression rate of disease was positively correlated with age at onset. Conclusions: SPG4 accounts for most of the AD-HSP cases in Taiwanese, with a frequency significantly higher than in other populations. SPAST mutations which predict complete loss of the spastin AAA cassette were associated with an earlier onset of disease.

Original languageEnglish
Article number216
JournalBMC Neurology
Volume14
Issue number1
DOIs
Publication statusPublished - Nov 25 2014
Externally publishedYes

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Hereditary Spastic Paraplegia
Mutation
Disease Progression
Genes
Genetic Association Studies
Age of Onset
Neurodegenerative Diseases
Lower Extremity

Keywords

  • AAA cassette
  • Hereditary spastic paraplegia
  • SPAST
  • Spastin
  • SPG4

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia. / Lan, Min Yu; Chang, Yung Yee; Yeh, Tu Hseuh; Lai, Szu Chia; Liou, Chia Wei; Kuo, Hung Chou; Wu, Yih Ru; Lyu, Rong Kuo; Hung, Jen Wen; Chang, Ying Chao; Lu, Chin Song.

In: BMC Neurology, Vol. 14, No. 1, 216, 25.11.2014.

Research output: Contribution to journalArticle

Lan, MY, Chang, YY, Yeh, TH, Lai, SC, Liou, CW, Kuo, HC, Wu, YR, Lyu, RK, Hung, JW, Chang, YC & Lu, CS 2014, 'High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia', BMC Neurology, vol. 14, no. 1, 216. https://doi.org/10.1186/s12883-014-0216-x
Lan, Min Yu ; Chang, Yung Yee ; Yeh, Tu Hseuh ; Lai, Szu Chia ; Liou, Chia Wei ; Kuo, Hung Chou ; Wu, Yih Ru ; Lyu, Rong Kuo ; Hung, Jen Wen ; Chang, Ying Chao ; Lu, Chin Song. / High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia. In: BMC Neurology. 2014 ; Vol. 14, No. 1.
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AU - Lan, Min Yu

AU - Chang, Yung Yee

AU - Yeh, Tu Hseuh

AU - Lai, Szu Chia

AU - Liou, Chia Wei

AU - Kuo, Hung Chou

AU - Wu, Yih Ru

AU - Lyu, Rong Kuo

AU - Hung, Jen Wen

AU - Chang, Ying Chao

AU - Lu, Chin Song

PY - 2014/11/25

Y1 - 2014/11/25

N2 - Background: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs. Methods: A total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed. Results: Mutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20 ± 18 years) compared with those with preservation of partial or total AAA cassette (32 ± 19 years, p = 0.041). For those with SPG4 mutations, disease severity was related to the patients' current age, and the progression rate of disease was positively correlated with age at onset. Conclusions: SPG4 accounts for most of the AD-HSP cases in Taiwanese, with a frequency significantly higher than in other populations. SPAST mutations which predict complete loss of the spastin AAA cassette were associated with an earlier onset of disease.

AB - Background: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs. Methods: A total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed. Results: Mutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20 ± 18 years) compared with those with preservation of partial or total AAA cassette (32 ± 19 years, p = 0.041). For those with SPG4 mutations, disease severity was related to the patients' current age, and the progression rate of disease was positively correlated with age at onset. Conclusions: SPG4 accounts for most of the AD-HSP cases in Taiwanese, with a frequency significantly higher than in other populations. SPAST mutations which predict complete loss of the spastin AAA cassette were associated with an earlier onset of disease.

KW - AAA cassette

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