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Lookup NU author(s): Professor Matthew CollinORCiD
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© 2017 by The American Society of Hematology. The SAMD9L gene and its paralog SAMD9, sitting head to tail on chromosome 7q, are among the notable absences in -7/7q- myelodysplastic syndromes (MDSs). As with many other genes harboring somatic mutation in neoplasia, germ line variants often provide critical insights into the mechanisms of dysfunction. In this issue of Blood, Tesi et al provide tantalizing new details to the story of SAMD9L mutation and familial -7/7q- syndromes.1 This widely expressed protein normally functions to inhibit proliferation and is therefore a potential tumor suppressor gene. The authors find 2 novel gain-of-function (GoF) variants that are associated with cytopenias, immunodeficiency, and neurological dysfunction and show how these can be ameliorated by coinherited loss-of-function alleles, or by somatic reversion of the mutated alleles in the bone marrow. When the progenitor ecosystem fails to select benign revertant clones, a predisposition to -7/7q- MDS is observed, otherwise known as the familial condition of ataxia-pancytopenia syndrome (ATXPC; Mendelian Inheritance in Man no. 159550). Neurological consequences, although variable, are not remedial by reversion mutation.
Author(s): Collin M
Publication type: Note
Publication status: Published
Online publication date: 20/04/2017
Acceptance date: 02/04/2016
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology