Situs inversus totalis in a 96-year-old female cadaver: evidence pointing toward the two-cilia model

摘要

Situs inversus totalis is a complete transposition of the thoracic and abdominal organs and represents one of many laterality defects within the heterotaxy spectrum. Here we report a case of a 96-year-old female cadaver with situs inversus. Examination of the respective computed tomography images revealed situs inversus totalis with dextrocardia. A detailed dissection demonstrated the transposition of the viscera and confirmed complete reversal of the visceral organs without major anomalies. In order to gain insight into the etiology of the present anatomical anomaly, we performed a screen for the putative genetic variants in the coding regions (exomes) of the DNA extracted from the cadaveric tissue using Next Generation Sequencing (NGS) technology. The analysis of the data revealed the presence of genetic variants, DVL1, DNAH9, PKD1, and TRPV4, that are closely associated with the regulation of cilia structure and function. Aberrant cilia function has been proposed by other investigators to be a major cause of laterality defects. Because DNAH9 mutation could be linked to the impairment of motile primary cilia function and mutations in DVL1, PKD1, and TRPV4 to that of non-motile primary cilia, our data could provide evidence in support of the two-cilia model where a synergistic functioning of both cilia types is required for a proper activation of the asymmetrical Nodal cascade in the left lateral plate mesoderm thereby assuring a typical and complete asymmetrical patterning of visceral organs.