DNA Mutation Analysis in Heterotaxy

Heterotaxy refers to the abnormal arrangement of internal organs in relation to each other. It is characterized by complex cardiac malformations that are thought to result from abnormal left-right patterning in early embryonic development. Mutations in four genes have been identified in human heterotaxy. ZIC3 , a zinc finger transcription factor, causes X-linked heterotaxy. EGF-CFC, ACVR2B , and LEFTYA are all members of a transforming growth factor-β signal transduction pathway that is critical for proper left-right development. Point mutations have been identified in each of these genes using polymerase chain reaction-based mutation analysis strategies. ZIC3 mutation screening will be used to illustrate the methods for molecular sequence data acquisition and examination. These techniques are applicable to any gene of interest and will be useful for further evaluation of candidate genes for heterotaxy.