Two patients with MIRAGE syndrome lacking haematological features: role of somatic second-site reversion SAMD9 mutations

MIRAGE syndrome is a life-threatening congenital disorder caused by deleterious SAMD9 mutations. In MIRAGE syndrome patients, multiple organ systems, including the haematopoietic system, are affected. We experienced two atypical MIRAGE syndrome patients who did not have any haematopoietic problems. In leukocyte DNA samples of the two patients, not only a deleterious SAMD9 mutation, but also another SAMD9 mutation that presumably abolishes the deleterious effect of the mutation (i.e., reversion mutation) was identified. Our observations indicate that a single cell that acquire a reversion mutation can outgrow in the hematopoietic cell pool, resulting in full reversion of the haematopoietic system. (By Dr. Satoshi Narumi, http://jmg.bmj.com/content/early/2017/11/24/jmedgenet-2017-105020 )