Recurrent de novo c.316G>A mutation in NIPA1 hotspot.
Mutations in the NIPA1 cause autosomal dominant form of hereditary spastic paraplegia. Allelic heterogeneity of known NIPA1 mutations is quite limited and the most common mutation is c.316G>A resulting in p.G106R protein change. Here we report the first direct evidence of de novo c.316G>A mutation in the same hotspot of the gene in two unrelated patients who had otherwise a prototypical NIPA1-associated phenotype with a severe form of uncomplicated spastic paraplegia. De novo nature of these mutations was confirmed by sequencing both sets of clinically unaffected parents and confirmation of paternity. We also discuss likely molecular mechanisms accounting for recurrent mutations in this segment of the gene. Apparently sporadic patients without a positive family history of hereditary spastic paraplegia need to be also evaluated for possible disease-causing mutations in genes that are inherited in an autosomal dominant fashion.
Department of Neurology, Vanderbilt University, Nashville, TN, United States. Electronic address: peter.hedera@vanderbilt.edu.
Peter
P
Hedera
D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
D008565:Membrane Proteins; C478824:NIPA1 protein, human
Apparently sporadic; Autosomal dominant; De novo mutation; Hereditary spastic paraplegia; NIPA1; Spinal cord atrophy