Childhood-Onset Spastic Paraplegia With NIPA1 Gene Mutation

Abstract

Hereditary spastic paraplegia is a heterogeneous group of inherited neurodegenerative disorders in which the predominant clinical feature is gait disturbance owing to spasticity and weakness of the lower limbs. Autosomal dominant hereditary spastic paraplegia is the predominant form of the disorder. To date, 10 autosomal dominant hereditary spastic paraplegia gene loci and genes for 6 of them have been identified. Spastic paraplegia 6, with a typical teenage onset and considered to be one of the more severe forms of the disease, is due to mutations in the gene NIPA1. We report a childhood-onset, aggressive, spastic paraparesis in a North American family with a c.316G>A mutation of the NIPA1 gene, confirming c.316 as a mutational hot spot. (J Child Neurol 2006;21:974—977; DOI 10.2310/ 7010.2006.00236).

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References

Fink JK : Hereditary spastic paraplegias: Nine genes and counting. Arch Neurol 2003;60:1045—1049.

Windpassinger C. , Auer-Grumbach M. , Irobi J. , et al: Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome . Nat Genet 2004;36:271—276.

Rainier S. , Chai J-H. , Tokarz D. , et al: NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Am J Hum Genet 2003;73:967—971.

Fink JK , Sharp GB , Lange BM , et al: Autosomal dominant, familial spastic paraplegia, type I: Clinical and genetic analysis of a large North American family. Neurology 1995;45:325—331.

Chen S. , Song C. , Guo H. , et al: Distinct novel mutations affecting the same base in the NIPA1 gene cause autosomal dominant hereditary spastic paraplegia in two Chinese families . Hum Mutat 2005;25:135—141.

Reed JA , Wilkinson PA , Patel H. , et al: A novel NIPA1 mutation associated with pure form of autosomal dominant hereditary spastic paraplegia. Neurogenetics 2005;6:79—84.

Chai J-H. , Locke DP , Greally JM , et al: Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons . Am J Hum Genet 2003;73:898—925.

Crosby AH , Proukakis C. : Is the transportation highway the right road for hereditary spastic paraplegia ? Am J Hum Genet 2002;71:1009—1016.

Lefevre C. , Bouadjar B. , Karaduman A. , et al: Mutations in ichthyin, a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 2004;13:2473—2482.