Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia.
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.
Simpson
Michael A
MA
Department of Medical Genetics, St. George's Hospital Medical School, University of London, London, United Kingdom.
Cross
Harold
H
Proukakis
Christos
C
Pryde
Anna
A
Hershberger
Ruth
R
Chatonnet
Arnaud
A
Patton
Michael A
MA
Crosby
Andrew H
AH
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000002:abnormalities / Q000000981:diagnostic imaging; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011487:Protein Conformation; D033303:Protestantism; D011859:Radiography; D015419:Spastic Paraplegia, Hereditary / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D013577:Syndrome
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C424703:SPG21 protein, human