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.
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.
Authors: Tyler Mark Pierson; Dimitre R Simeonov; Murat Sincan; David A Adams; Thomas Markello; Gretchen Golas; Karin Fuentes-Fajardo; Nancy F Hansen; Praveen F Cherukuri; Pedro Cruz; James C Mullikin; Craig Blackstone; Cynthia Tifft; Cornelius F Boerkoel; William A Gahl Journal: Eur J Hum Genet Date: 2011-12-07 Impact factor: 4.246
Authors: Kathleen A Potter; Michael J Kern; George Fullbright; Jacek Bielawski; Steven S Scherer; Sabrina W Yum; Jian J Li; Hua Cheng; Xianlin Han; Jagadish Kummetha Venkata; P Akbar Ali Khan; Bärbel Rohrer; Hiroko Hama Journal: Glia Date: 2011-04-13 Impact factor: 7.452
Authors: Roshan Koul; Fathiya M Al-Murshedi; Faisal M Al-Azri; Ranjit Mani; Rana A Abdelrahim; Vivek Koul; Amna M Alfutaisi Journal: Sultan Qaboos Univ Med J Date: 2013-06-25
Authors: Frans Brugman; Hans Scheffer; H Jurgen Schelhaas; Willy M Nillesen; John H J Wokke; Bart P C van de Warrenburg; Leonard H van den Berg Journal: J Neurol Date: 2009-03-01 Impact factor: 4.849