Rainier Shirley, Sher Carron, Reish Orit, Thomas Donald, Fink John K
Department of Neurology, University of Michigan, Ann Arbor, USA.
Arch Neurol. 2006 Mar;63(3):445-7. doi: 10.1001/archneur.63.3.445.
Mutations in the SPG3A gene (atlastin protein) cause approximately 10% of autosomal-dominant hereditary spastic paraplegia. For many subjects with an SPG3A mutation, spastic gait begins in early childhood and does not significantly worsen even over many years. Such subjects resemble those with spastic diplegic cerebral palsy. To date, only 9 SPG3A mutations have been reported.
To analyze the SPG3A coding sequence in an individual with childhood-onset spastic gait, who, prior to the birth of her similarly affected child, had no previous family history of hereditary spastic paraplegia.
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.
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.
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.
SPG3A基因（atlastin蛋白）突变导致约10%的常染色体显性遗传性痉挛性截瘫。对于许多携带SPG3A突变的患者，痉挛性步态始于儿童早期，甚至多年都不会明显恶化。这些患者与痉挛性双侧瘫脑瘫患者相似。迄今为止，仅报道了9种SPG3A突变。
分析一名儿童期起病的痉挛性步态患者的SPG3A编码序列，该患者在其同样患病的孩子出生前，家族中无遗传性痉挛性截瘫病史。
通过对先证者、其患病孩子、未患病父母及对照者的DNA样本进行聚合酶链反应扩增每个外显子，随后进行直接DNA测序，分析SPG3A编码序列。扩增并分析17个微卫星多态性以确认所报道的亲子关系。
我们在先证者及其患病孩子中鉴定出一种新的SPG3A突变（L157W）。该突变在先证者未患病的父母中不存在。微卫星多态性分析结果与所报道的亲子关系一致。这些结果表明该新的SPG3A突变是在先证者中新生的。
我们报道了一名儿童期起病、非进行性、痉挛性双侧瘫患者中新生的一种新的SPG3A突变，该患者在其同样患病的儿子出生前家族中无遗传性痉挛性截瘫病史。尽管罕见，但对于未发现其他病因的痉挛性双侧瘫脑瘫患者，必须考虑新生遗传性痉挛性截瘫基因突变的发生。这对于正确的遗传咨询极为重要，因为检测到突变时复发风险可能高达50%。
