Study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized.
The mutation of the spatacsin gene (SPG11) is the single most commoncause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene.
The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria.The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed.
Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival.
The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.
SOURCE: Brain Advance Access published online on January 28, 2010
Antonio Orlacchio1,2, Carla Babalini1, Antonella Borreca1,2, Clarice Patrono1, Roberto Massa1,2, Sarenur Basaran3, Renato P. Munhoz4, Ekaterina A. Rogaeva5,6, Peter H. St George-Hyslop5,6,7, Giorgio Bernardi1,2 and Toshitaka Kawarai8
1 Laboratorio di Neurogenetica, CERC-IRCCS Santa Lucia, Rome, Italy
2 Dipartimento di Neuroscienze, Università di Roma ‘Tor Vergata’, Rome,
3 Department of Medical Genetics, Istanbul University Cerrahpasa School
of Medicine, Istanbul, Turkey
4 Department of Neurology, Federal University of Paraná, Curitiba, PR,
5 Centre for Research in Neurodegenerative Diseases, University of
Toronto, Toronto, ON, Canada
6 Department of Medicine, University of Toronto, Toronto, ON, Canada
7 Department of Clinical Neurosciences, University of Cambridge,
8 Department of Neurology, Hyogo Brain and Heart Centre, Himeji City,