The genetic causes of some forms of cleft lip and palate are described in two reports in the October issue of Nature Genetics (Vol. 29, Issue 2, 01 Oct 01). The discoveries offer important insights into human development and the mechanisms involved in a class of common birth defects about which surprisingly little is known.
Cleft lip and/or palate forms when structures around the mouth fail to come together properly during early human development. Such defects are seen, often in combination with other abnormalities, in about 0.4 to 2 babies out of 1,000 who are born. While some cases of cleft lip and/or palate are inherited, most occur in individuals with no family history of disease (sporadic cases), and are believed to be a result of both genetic and environmental factors.
In the first report, Philip Stanier and colleagues at Imperial College, London, identified a gene (TBX22) important for the proper growth of structures in the face, which, when mutated, causes a type of cleft palate defect that is inherited through the X chromosome. The same mutation was detected in several families from different ethnic backgrounds who were affected by the disease. In the second paper, Richard Spritz and colleagues at the University of Colorado, in collaboration with scientists in Venezuela, identified a variant of another gene (PVRL1) that predisposes individuals from a population in northern Venezuela to a sporadic cleft lip and palate defect. Previously, the scientists had found that mutations in the same gene, which is important for cell fusion during development, causes an inherited cleft lip and palate syndrome in another small population in Venezuela. Thus, the same gene can contribute to both inherited and sporadic forms of the disease. Together the two reports provide clues to the causes underlying human developmental defects.
The significance of the findings are summarized in an accompanying News & Views article by Jeffrey Murray of the University of Iowa, in which the author points out that research into birth defects has been slow since these diseases are not "attractive candidates for study by the large corporate enterprises that increasingly serve as the engines of gene mapping and product development".
Dr. Philip Stanier
Institute of Reproductive and Developmental Biology, Imperial College, London, UK
Tel: +44 20 7594 2124
Dr. Richard A. Spritz
University of Colorado Health Sciences Center, Denver, USA
Tel: +1 303 315 0409
Additional contact for comment on paper:
Dr. Jeffrey C. Murray
Department of Pediatrics, University of Iowa, USA
Tel: +1 319 335 6897
(C) Nature Genetics press release.
Message posted by: Trevor M. D'Souza