A HOMEOBOX GENE, HLXB9, IS THE MAJOR LOCUS FOR DOMINANTLY INHERITED SACRAL AGENESIS

Partial absence of the sacrum is a rare congenital defect which also o ccurs as an autosomal dominant trait; association with anterior mening ocoele. presacral teratoma and anorectal abnormalities constitutes the Currarino triad(1) (MIM 176450). Malformation at the caudal end of th e developing notochord at approximately Carnegie stage 7 (16 post-ovul atory days). which results in aberrant secondary neurulation. can expl ain the observed pattern of anomalies(2,4). We previously reported lin kage to 7q36 markers in two dominantly inherited sacral agenesis famil ies(2). We now present data refining the initial subchromosomal locali zation in several additional hereditary sacral agenesis (HSA) families . We excluded several candidate genes before identifying patient-speci fic mutations in a homeobox gene, HLXB9 which was previously reported to map to 1q41-q42.1 and to be expressed in lymphoid and pancreatic ti ssues(5,6).