SPG3A-hereditary spastin paraplegia with genetic anticipation and incomplete penetrance / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the SPG3A coding sequence and clinical features in a family with dominantly inherited hereditary spastin paraplegia (HSP) characterized by incomplete genetic penetrance and genetic anticipation.</p><p><b>METHODS</b>Analysis of the SPG3A coding sequence, being sequence variations in SPG4/spastin (S44L and P45Q) and SPG6/nipa1([GCG]5-11) genes were performed for the proband, his affected son, his unaffected parents and unaffected brother. One hundred normal individuals were selected as controls.</p><p><b>RESULTS</b>SPG3A mutation V253I in the proband, his affected son, and unexpectedly, in his asymptomatic, 72 year old father was identified. No mutation at the same site was found in the other members of this family as well as the control.</p><p><b>CONCLUSION</b>Incomplete genetic penetrance due to SPG3A mutation V253I was observed in this family. This is the second report. Marked phenotype variation (genetic non-penetrance, adult versus childhood onset symptoms) between subjects with the same SPG3A mutation indicates the influence of modifying genetic or environmental factors. Progressively earlier symptom onset and increasing symptom severity in this family is consistent with genetic anticipation which has not been previously reported in SPG3A-HSP.</p>