Copyright © 2003 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 73, Issue 5, 1147-1156, 1 November 2003
doi:10.1086/379522
Maspardin Is Mutated in Mast Syndrome, a Complicated Form of Hereditary Spastic Paraplegia Associated with Dementia
Michael A. Simpson1, Harold Cross3, Christos Proukakis1, 2, Anna Pryde1, Ruth Hershberger4, Arnaud Chatonnet5, Michael A. Patton1 and Andrew H. Crosby1, 
, 
1 Department of Medical Genetics, St. George’s Hospital Medical School, University of London, Royal Free and University College Medical School, London
2 Department of Clinical Neurosciences, Royal Free and University College Medical School, London
3 Department of Ophthalmology, University of Arizona School of Medicine, Tucson
4 Windows of Hope Genetic Studies, Baltic, OH
5 Departement de Physiologie Animale, Institut National de la Recherche Agronomique, Montpellier, France
Address for correspondence and reprints: Dr. Andrew H. Crosby, Department of Medical Genetics, St. George’s Hospital Medical School, University of London, Cranmer Terrace, London SW17 0RE, United KingdomAbstract
Mast syndrome is an autosomal recessive, complicated form of hereditary spastic paraplegia with dementia that is present at high frequency among the Old Order Amish. Subtle childhood abnormalities may be present, but the main features develop in early adulthood. The disease is slowly progressive, and cerebellar and extrapyramidal signs are also found in patients with advanced disease. Patients have a thin corpus callosum and white-matter abnormalities, as seen on magnetic resonance imaging. Using an extensive Amish pedigree, we have mapped the Mast syndrome locus (SPG21) to a small interval of chromosome 15q22.31 that encompasses just three genes. Sequence analysis of the three transcripts revealed that all 14 affected cases were homozygous for a single base-pair insertion (601insA) in the acid-cluster protein of 33 kDa (ACP33) gene. This frameshift results in the premature termination (fs201-212X213) of the encoded product, which is designated “maspardin” (Mast syndrome, spastic paraplegia, autosomal recessive with dementia), and has been shown elsewhere to localize to intracellular endosomal/trans-Golgi transportation vesicles and may function in protein transport and sorting.
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