A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23

K. J. Dick, R. Al-Mjeni, W. Baskir, R. Koul, M. A. Simpson, M. A. Patton, S. Raeburn, A. H. Crosby

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous neurodegenerative disorders in which the cardinal pathologic feature is upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. To date, 14 autosomal recessive HSP loci have been mapped. Methods: We have identified a large consanguineous Omani family in which an autosomal recessive form of HSP is segregating. The age at onset varied from 6 to 11 years and the course of the disease is progressive with intellectual disability and is associated with seizures in two individuals. To map the chromosomal location of the causative gene we undertook 250K gene chip SNP analyses of all affected individuals assuming that a founder mutation was responsible. Results: All affected individuals shared a 20.4 Mb (3.25 cM) region of homozygosity located on chromosome 16q21-q23.1, defined by SNP markers rs149428 and rs9929635 (peak multipoint lod score of 4.86). Two candidate genes, dynein, cytoplasmic 1, light intermediate chain 2 (DYNC1LI2) and vacuolar protein sorting 4 homolog A (VPS4A), were sequenced but no disease causing mutations were identified. Conclusion: We have mapped the chromosomal location of a novel gene responsible for a form of hereditary spastic paraplegia (HSP) (SPG35) and defined its clinical presentation.

Original languageEnglish
Pages (from-to)248-252
Number of pages5
JournalNeurology
Volume71
Issue number4
DOIs
Publication statusPublished - Jul 22 2008

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Hereditary Spastic Paraplegia
Single Nucleotide Polymorphism
Cytoplasmic Dyneins
Genes
Lod Score
Nerve Degeneration
Mutation
Motor Neurons
Protein Transport
Oligonucleotide Array Sequence Analysis
Age of Onset
Intellectual Disability
Neurodegenerative Diseases
Lower Extremity
Seizures
Chromosomes
Light

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Dick, K. J., Al-Mjeni, R., Baskir, W., Koul, R., Simpson, M. A., Patton, M. A., ... Crosby, A. H. (2008). A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23. Neurology, 71(4), 248-252. https://doi.org/10.1212/01.wnl.0000319610.29522.8a

A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23. / Dick, K. J.; Al-Mjeni, R.; Baskir, W.; Koul, R.; Simpson, M. A.; Patton, M. A.; Raeburn, S.; Crosby, A. H.

In: Neurology, Vol. 71, No. 4, 22.07.2008, p. 248-252.

Research output: Contribution to journalArticle

Dick, KJ, Al-Mjeni, R, Baskir, W, Koul, R, Simpson, MA, Patton, MA, Raeburn, S & Crosby, AH 2008, 'A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23', Neurology, vol. 71, no. 4, pp. 248-252. https://doi.org/10.1212/01.wnl.0000319610.29522.8a
Dick, K. J. ; Al-Mjeni, R. ; Baskir, W. ; Koul, R. ; Simpson, M. A. ; Patton, M. A. ; Raeburn, S. ; Crosby, A. H. / A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23. In: Neurology. 2008 ; Vol. 71, No. 4. pp. 248-252.
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