A novel FOXC2 mutation in spinal extradural arachnoid cyst

Abstract

Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal, which causes spinal cord compression and subsequent neurological damage. We previously identified two FOXC2 mutations in two SEDAC families. The FOXC2 mutations have been shown to be responsible for lymphedema-distichiasis syndrome (LDS), which includes SEDAC as an occasionally associated phenotype. We encountered a non-familial patient with SEDAC associated with LDS, and identified a novel nonsense mutation in FOXC2, c.349C>T (p.Q117*).

Figure 1

Spinal extradural arachnoid cyst. T2-weighted image of magnetic resonance imaging (MRI) scan. There are multiple cysts (asterisk marks) dorsal to the spinal cord at the thoracic spine.

Figure 2

FOXC2 mutations in spinal extradural arachnoid cyst. (a) Electrophoreogram of the wild type FOXC2 (upper panel) and heterozygous nonsense mutation c.349C>T (Q117*) in the present patient (lower panel). (b) Amino-acid sequences around p.Q117 of the FOXC2 in different species. p.Q117 is highly conserved. (c) Protein structure of FOXC2 and positions of the present (blue letters) and previously identified (black letters) mutations in spinal extradural arachnoid cyst. (d) Dual luciferase assay. Promoter activities of wild type (WT) and Q117* FOXC2 vectors and the empty vector (NC). The activity of Q117* FOXC2 was significantly decreased compared with that of WT FOXC2 (Asterisk: P<0.01 (t-test), thick bar: mean value, error bar: s.e.).