Germline and somatic mosaicism in achondroplasia: Figure 1

the possible eVects of shared ancestry and exercise on the clinical expression of a specific mutation, especially in subpopulation groups with known founder eVects.Although these examples of divergent phenotypic expression in kindred 101a and the twins in pedigree 138 are based on small numbers, they lend support to the notion that HCM is not a simple monogenic disorder and that both genetic and environmental factors are modifiers of the disease phenotype.A strategy followed in studies of disease phenotypes with multifactorial aetiology is to reduce the complexity of analysis by investigating genetically homogeneous subjects.The presence of the founder MYH7 A797T mutation suggests that the families harbouring it share a degree of common ancestry.We therefore propose that the presence of this HCM causing mutation with incomplete penetrance, in a substantial group of related people, provides an opportunity to investigate the role of additional factors involved in the development of the disease phenotype.Only when these factors are known will the puzzling variability in the clinical expression which is a feature of HCM mutations, and the true pathophysiology of this disease, be understood.