Abstract | BACKGROUND: OBJECTIVE: METHODS: The SPG3A coding sequence was analyzed in DNA samples from the proband, her affected child, her unaffected parents, and control subjects by polymerase-chain-reaction amplification of each exon followed by direct DNA sequencing. Seventeen microsatellite polymorphisms were amplified and analyzed to confirm reported paternity. RESULTS: We identified a novel SPG3A mutation (L157W) in the proband and her affected child. This mutation was absent in the proband's unaffected parents. Results of microsatellite polymorphism analysis were consistent with paternity as reported. These results indicate that this novel SPG3A mutation arose de novo in the proband. CONCLUSIONS: We report the de novo occurrence of a novel SPG3A mutation in a subject with childhood-onset, nonprogressive, spastic diplegia who had no previous family history of hereditary spastic paraplegia until the birth of her similarly affected son. Although rare, the occurrence of a de novo hereditary spastic paraplegia gene mutation must be considered in subjects with spastic diplegic cerebral palsy for whom no other cause is identified. This is extremely important for correct genetic counseling because recurrence risk may be as high as 50% when a mutation is detected.
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Authors | Shirley Rainier, Carron Sher, Orit Reish, Donald Thomas, John K Fink |
Journal | Archives of neurology
(Arch Neurol)
Vol. 63
Issue 3
Pg. 445-7
(Mar 2006)
ISSN: 0003-9942 [Print] United States |
PMID | 16533974
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Membrane Proteins
- Tryptophan
- ATL1 protein, human
- GTP Phosphohydrolases
- GTP-Binding Proteins
- Leucine
|
Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Cerebral Palsy
(genetics)
- DNA Mutational Analysis
(methods)
- Family Health
- Female
- GTP Phosphohydrolases
(genetics)
- GTP-Binding Proteins
- Humans
- Leucine
(genetics)
- Male
- Membrane Proteins
- Middle Aged
- Mutation
- Tryptophan
(genetics)
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