Possible anticipation in hereditary spastic paraplegia type 4 (SPG4).
OBJECTIVE
We report a multigenerational family with uncomplicated hereditary spastic paraplegia type 4 and apparent anticipation. Genetic analysis of the proband revealed a frame shift mutation (5 base pair deletion) in exon 9 of the SPG4 gene encoding the spastin protein. We hypothesized that this deletion mutation may be dynamic and variability in the size of the deletion could account for the anticipation.


METHODS
Clinical and genetic analysis of this family and the deletion mutation.


RESULTS
In this family, the age of onset, which ranges from 3 to 50 years shows an average decrease in the age of onset of 21.8 years per transmission over three generations. Genetic analysis of multiple family members indicates that all affected members carry the same c.1340_1344delTATAA mutation and that it is not dynamic.


CONCLUSIONS
In this family, other molecular mechanisms may contribute to development of anticipation.
Reddy
P Leema
PL
New Jersey Neuroscience Institute, JFK Medical Center, Edison, New Jersey 08820, USA.
Seltzer
William K
WK
Grewal
Raji P
RP
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D020132:Anticipation, Genetic / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human