Molecular genetic investigation of autosomal dominant hemifacial microsomia

The overall purpose of this project was to explore the underlying pathogenesis of Hemifacial microsomia (HFM), investigate treatment and management options identify likely candidate genes and screen candidate genes for mutation(s) causing the form of HFM segregating on chromosome 11 in a West Australian family. Hemifacial microsomia is a congenital malformation arising from the derivatives of the first and second branchial arches. It is both clinically and genetically heterogeneous and can occur sporadically or segregate within families in an autosomal fashion. HFM is characterised by significant undergrowth to one side of the face and is a common birth defect with an estimated incidence of 1 in 1,000 to 1 in 5.600 births. Most HFM cases are sporadic, but there are rare familial cases that exhibit autosomal dominant inheritance. These families present the best opportunity for locating and identifying HFM mutations. Two autosomal dominant forms of this disease have been located, one to a 10.7 million DNA base region on chromosome 14 and the other to an 18.8 million base region on chromosome 11. The identification and cooperation of a large West Australian family with HFM has allowed the phenotypic and genotypic study of the disorder presented in this thesis. Candidate genes were identified from the Draft Human Genome through genome mining and bioinformatics tools. This essentially involved cross-tabulating the genes and predicting genes I the two known hemifacial microsomia candidate regions and by comparison of gene names, aliases, acronyms, functions, disease associations (particularly with axial asymmetry), timing of expression and trinucleotide repeat expansions (chromosome 11 hemifacial microsomia appears to show anticipation). The chromosome 11 linkage region was also investigated for homologies to the Completed Mouse Genome. This project has greatly contributed to the fundamental understanding of this disease and its phenotype and provides a basis for further studies aimed at better diagnosis, treatment and identification of causative genes and other factors.

Grantor dc:publisher

Edith Cowan University, Research Online, Perth, Western Australia

Year dc:date

2004

Author dc:creator

• Watt, Rebecca

• Hemifacial microsomia
• Face
• Abnormalities
• Genetic aspects.
• Medical Sciences

Repository record dc:identifier

https://ro.ecu.edu.au/theses/787

OAI identifier oai:identifier

oai:ro.ecu.edu.au:theses-1788