A third condition, the Carney-Stratakis syndrome (CSS), describes the dyad of hereditary gastrointestinal stromal tumor (GIST) and paraganglioma, that is caused by germline mutations in the mitochondrial tumor suppressor gene pathway involving the succinate dehydrogenase subunits SDHD, SDHC and SDHB.
In 40-50% of cases, the disorder has been linked with germline mutations in the CDKN2A gene, which codes for p16 (a regulator of cell division).
These include, in descending order of frequency, neurofibromatosis Recklinghausen (NF-1), Carney's triad (gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma), germline gain-of-function mutations in c-Kit/PDGFRA, and the Carney-Stratakis syndrome.
However, also a PNH case with a germline mutation in the autosomal gene PIGT and a second acquired somatic hit has been reported.
He reevaluates August Weismann's model of the cell compartmentalization of somatic and germline cell lineages (see Weismann barrier), and argues that the vision of the individual taken by the modern synthesis is insufficient to explain the early evolution of development or ontogeny.
Short RNAs are well-known to silence TEs (transposable elements) through the RNAi (RNA interference) pathway, and Piwi-associated RNAs (piRNAs) play a crucial role in transposon silencing in the germline.
Recent studies have shown that many cases of Sertoli Leydig cell tumor of the ovary are caused by germline mutations in the DICER1 gene.