CHARACTERIZATION AND PHYSICAL MAPPING IN HUMAN AND MOUSE OF A NOVEL RING FINGER GENE IN XP22

Microphthalmia with linear skin defects (MLS) is an X-linked dominant male-lethal syndrome caused by different deletions of chromosome Xp22. Through the screening of cDNA libraries with the cross-species conser ved marker 61B3-R (DXS1141), we identified a new gene at the telomeric breakpoint of the MLS critical region, which encodes a transcript con taining a RING finger domain. This novel gene was independently cloned by another group and found to be mutated in Opitz syndrome. In this s tudy we characterized the expression pattern of this gene, identified various splice variants, delineated its exon-intron boundaries, and de termined that it is not mutated in either Aicardi or Goltz syndrome, t wo X-linked dominant conditions with phenotypes that overlap with that of MLS syndrome. This novel RING finger gene is expressed throughout mouse embryonic development, with the highest levels of expression in E7--E11. FISH and hybridization to mouse YACs confirmed human and mous e synteny in the order of this gene and other genes in the MLS critica l region; however, this gene spans the boundary of the pseudoautosomal region ill mouse but not in humans. (C) 1998 academic Press.