FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules

Opitz G/BBB syndrome (OS) is a genetically heterogeneous disorder with an X -linked locus and an autosomal locus linked to 22q11.2. OS affects multiple organ systems with often variable severity even between siblings. The clin ical features, which include hypertelorism, cleft lip and palate, defects o f cardiac septation, hypospadias, and anorectal anomalies, indicate an unde rlying disturbance of the developing ventral midline of the embryo. The gen e responsible for X-linked OS, FXY/2MID1, is located on the short arm of th e human X chromosome within Xp22.3 and encodes a protein with both an RBCC (RING finger, B-box, coiled coil) and a B30.2 domain. The Fry gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, calle d FXY2, which also maps to the X chromosome within Xq22, The mouse Fxy2 gen e is located on the distal part of the mouse X chromosome within a region s yntenic to Xq22, Analysis of genes flanking both FXY/MID1 and FXY2 (as well as their counterparts in mouse) suggests that these regions may have arise n as a result of an intrachromosomal duplication on an ancestral X chromoso me. We have also identified in both FXY2 and FXY/MID1 proteins a conserved fibronectin type III domain located between the RBCC and B30.2 domains that has implications for understanding protein function. The FXY/MID1 protein has previously been shown to colocalize with microtubules, and here we show that the FXY2 protein similarly associates with microtubules in a manner t hat is dependent on the carboxy-terminal B30.2 domain. (C) 1999 Academic Pr ess.