Genetic Analysis of Limb Malformation Disorders: Freeman Sheldon Syndrome Exome Sequencing Study (LMD-FSS)

The overall goal of this project is to investigate the etiology and pathogenesis of malformations (i.e., birth defects) of the limb, concentrating on abnormalities of limb patterning such as limb deficiency/duplications and multiple congenital contractures. The exome sequences of four unrelated individuals were obtained by massively parallel DNA sequencing. The three individuals were affected with Freeman Sheldon syndrome (OMIM: 193700).]]>
Inclusion: Four affected, unrelated individuals with Freeman Sheldon syndrome. Exclusion: None.]]>
Freeman Sheldon syndrome (FSS) is a very rare disease with autosomal dominant inheritance. The selected individuals have a known mutation in MYH3, which is the causative gene in >90% of FSS cases. Therefore, as a proof of concept experiment, a hypothesis was made that this gene would be identifiable as a gene common to all four individuals with Freeman Sheldon syndrome, wherein each individual had one novel, protein-changing variant in the gene when filtered against public SNP databases and HapMap exomes. One individual from whom exome sequence was obtained did not consent for deposition of the data into dbGaP and is excluded from the dataset.]]>