X-chromosomal gekoppelte Lippen-Kiefer-Gaumenspalten: Molekulare Untersuchung durch Positionsklonierung

• Applicant: Professor Dr. Hans Hilger Ropers
• Subject Area: Human Genetics
• Term: from 1995 to 2002
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5231128

Cleft lip an palate is a common malformation which occurs as an isolated clinical feature but also in numerous complex malformation syndromes. Almost all non-syndromic forms are multifactorial and very little is known about the genetic and environmental factors predisposing to this frequent disorder. This project aims at the molecular and functional elucidation of the genetic defects underlying three monogenic forms of facial clefting,I. non-syndromic X-linked cleft palate (CPX) at Xq21,II. a syndrome consisting of facial and mental retardation which has been observed in two patients with X-linked inversions and a matching breakpoint at Xp11.2III. and X-linked Opitz syndrome, a clinically complex midline defect with cleft lip and palate which is due to mutations in the MID1 RING finger gene that we have recently cloned. Functional studies have shown that the MID1 protein plays a role in the assembly and stabilization of microtubules. Elucidation of the pathogenetic roles of these genes in facial clefting may provide a clue to the underlying environmental factors, with important consequences for prevention.

• DFG Programme: Priority Programmes
• Subproject of: SPP 313: Molekulare Dysmorphogenese