Pedigree Analysis Paper

The pedigree analysis reveals that the condition affects both sexes, is present in all generations and can only be inherited from an affected mother. These features, allied to the absence of male transmission to the offspring, rule out Y-linked and autosomal inheritances. If it was an X-linked dominant inheritance, an affected male would always have affected daughters, but II.6 has one unaffected daughter (III.6), so it can be ruled out.
The family pedigree seems to have a mitochondrial inheritance. This disorder is caused by mutations in the mitochondrial DNA (mtDNA), that can affect both sexes and it is strictly inherited from an affected mother. The expressivity of the condition may vary since the mitochondrial genome copies are quite unique and can be homoplasmy or heteroplasmy. Homoplasmy is when the cell has identical genome copies, whereas in the case of heteroplasmy, each cell can have the coexistence of mutant and wild-type mtDNA. When heteroplasmy is considered, for each mutation there is a specific critical threshold level of mutation (Taylor and Turnbull, 2005)⁠. Therefore, the individuals III.9 and III.10 don’t show the disease
Whole-genome sequencing plays an important role in identifying the causative genes, environmental factors need to be considered since they might affect the expression of the disease phenotype. There are many aspects that make for difficulty in predicting the outcome of each pregnancy and the penetrance effects of the condition, such as the copies of mutant mtDNA inherited (FIGURE 1), cellular heteroplasmy and cellular mosaicism (Taylor and Turnbull, 2005; Wai, Teoli and Shoubridge, 2008; Cao et al., 2009)⁠. It’s therefore necessary to achieve an accurate diagnosis of mutant mtDNA and a better understanding of disease mechanisms to provide preventive approaches and therapeutic targets (Taylor and Turnbull,