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Genetic Aspects of Cleft Lip and Palate

Author: Linda P. Jakobsen, MD, PhD

Date, Institution and University: 2006, Department of Plastic and Reconstructive Surgery and Burns, Rigshospitalet


The thesis is based on work performed at Wilhelm Johannsen Centre for Functional Genome Research and the Department of Plastic and Reconstructive Surgery and Burns, Rigshospitalet in the period 2003–2006. It comprises four studies.

The general aim of this thesis was to study genetic aspects of cleft lip and palate, which is a common and complex congenital malformation caused by environmental and genetic factors. This was achieved by studying in detail the Pierre Robin Sequence (PRS), which is a subgroup of the cleft lip and palate population. Moreover, the genetic aspects were studied by performing gene expression profiles in lip and palate tissue from patients with different types of cleft lip and/or palate (CL/P), and by carrying out a linkage study in a large CL/P multiplex family.

It was found, that part of the aetiology in PRS might be caused by dysregulation of the gene SOX9, and perhaps also the gene KCNJ2.

Expression of genes in lip and palate tissue suggests that the gene osteopontin (SPP1), and other genes normally related to the immune response may have a function in the development of the palate, a function that may differ according to the cleft palate type.

Finally, the genomewide linkage study in the CL/P multiplex family suggested linkage to a chromosomal region (1q32) close to, but not including a well-known CL/P gene, IRF6. It was suggested that this region may harbour genes or non-coding elements, regulating IRF6, although genes with a distinct function in CL/P development are a possibility too.

Together, the thesis point to several new candidate genes and signalling pathways potentially involved in the aetiology of PRS and CL/P.

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