Abstract：
SAMD9 and SAMD9L are two interferon-regulated genes located adjacent to each other on chromosome 7q21.2. Germline gain-of-function (GL GOF) mutations in SAMD9/SAMD9L are the genetic cause of MIRAGE syndrome, ataxia-pancytopenia (ATXPC) syndrome, myeloid leukemia syndrome with monosomy 7 (MLSM7), refractory cytopenia of childhood (RCC), transient monosomy 7 in children, SAMD9L-associated autoinflammatory disease (SAAD), and a proportion of inherited aplastic anemia and bone marrow failure syndromes. The myeloid neoplasms associated with GL GOF SAMD9/SAMD9L mutations have been included in the World Health Organization (WHO) 2022 classification. The discovery of SAMD9/SAMD9L-related diseases has revealed some interesting pathobiological mechanisms, such as a high rate of primary somatic compensation, with one of the mechanisms being (transient) monosomy 7 a mechanism also described as \"adaption by aneuploidy.\" The somatic compensation in the blood can complicate the diagnosis of SAMD9/SAMD9L-related disease when relying on hematopoietic tissues for diagnosis. Recently, GL loss-of function (LOF) mutations have been identified in older individuals with myeloid malignancies in accordance with a mouse model of SAMD9L loss that develops a myelodysplastic syndrome (MDS)-like disease late in life. The discovery of SAMD9/SAMD9L-associated syndromes has resulted in a deeper understanding of the genetics and biology of diseases/syndromes that were previously oblivious and thought to be unrelated to each other. Besides giving an overview of the literature, this review wants to also provide some practical guidance for the classification of SAMD9/SAMD9L variants that is complicated by the nonrecurrent nature of these mutations but also by the fact that both GL GOF, as well as loss-of-function mutations, have been identified.
摘要：
SAMD9和SAMD9L是位于染色体7q21.2上相邻的两个干扰素调节基因。SAMD9/SAMD9L中的种系功能获得突变是MIRAGE综合征的遗传原因，共济失调全血细胞减少综合征（ATXPC），髓系白血病综合征伴7型（MLSM7），儿童难治性血细胞减少症（RCC），儿童的一过性单体7，SAMD9L相关自身炎性疾病(SAAD)和一定比例的遗传性再生障碍性贫血和骨髓衰竭综合征。
