Figure 2.

Pedigree and partial chromatograms showing the SAMD9 mutations over time. The segregation of the gain of function (p.Thr778Ile) and the appearance of the reversion mutation (p.Arg221^*, p.Arg285^*) is shown over time. Above the time frame (corresponding to the age of the patient when DNA was sampled), next to the pedigree are shown a scheme of the haplotype in different cells: in blue is the wild type haplotype, in yellow the haplotype with a gain of function mutation and in green the haplotype with a gain of function disrupted by a loss of function mutation in cis. In the pedigree the symbol dashed indicates absence or correction of the symptoms found in MIRAGE syndrome. Under the time frame, partial Sanger chromatograms show presence or absence of the mutations at 5 days and 14 years of age for the proband. The reference sequence is highlighted in blue. At the 5 days old of the proband, the revertant mutation p.Arg221^* was found in cis in the mother but not transmitted to her children, confirming the adaptation mechanism in the mother occurred somatically and did not concern all tissues, at least the gonads. The correction of the symptoms around day 20 for the proband suggests the adaptive mechanism by appearance of the p.Arg285^* mutation was enough at this age, but it was only confirmed on a sample at 14 years old. WT, wild-type; gof, gain of function mutation; lof, loss of function mutation.