Chromosomal microdeletion syndromes present with a wide spectrum of clinical phenotypes that depend on the size and gene content of the affected region. In a healthy carrier, epigenetic mechanisms may compensate for the same microdeletion, which may segregate through several generations without any clinical symptoms until the epigenetic modifications no longer function. We report 2 novel cases of Xq24 microdeletions inherited from mothers with extremely skewed X-chromosome inactivation (sXCI). The first case is a boy presenting with X-linked mental retardation, Nascimento type, due to a 168-kb Xq24 microdeletion involving 5 genes (CXorf56, UBE2A, NKRF, SEPT6, and MIR766) inherited from a healthy mother and grandmother with sXCI. In the second family, the presence of a 239-kb Xq24 microdeletion involving 3 additional genes (SLC25A43, SLC25A5-AS1, and SLC25A5) was detected in a woman with sXCI and a history of recurrent pregnancy loss with a maternal family history without reproductive wastages or products of conception. These cases provide evidence that women with an Xq24 microdeletion and sXCI may be at risk for having a child with intellectual disability or for experiencing a pregnancy loss due to the ontogenetic pleiotropy of a chromosomal microdeletion and its incomplete penetrance modified by sXCI.

中文翻译：

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描述遗传性 Xq24 微缺失与母亲 sXCI 分离的临床表现：两例具有不同表型的新病例，范围从 UBE2A 缺陷综合征到复发性流产

染色体微缺失综合征具有广泛的临床表型，取决于受影响区域的大小和基因含量。在健康的携带者中，表观遗传机制可能会补偿相同的微缺失，这些微缺失可能会隔离几代而没有任何临床症状，直到表观遗传修饰不再起作用。我们报告了 2 例 Xq24 微缺失的新病例，这些病例从 X 染色体失活 (sXCI) 极度倾斜的母亲那里继承而来。第一个病例是一名男孩，由于 168-kb Xq24 微缺失涉及 5 个基因（CXorf56、UBE2A、NKRF、SEPT6 和 MIR766），因此患有 X 连锁精神发育迟滞，Nascimento 型，遗传自一位患有 sXCI 的健康母亲和祖母。在第二个家族中，存在涉及 3 个额外基因（SLC25A43、SLC25A5-AS1、和 SLC25A5) 在一名患有 sXCI 且有反复流产史且有母亲家族史的女性中检测到，没有生殖浪费或受孕产物。这些病例提供的证据表明，由于染色体微缺失的个体遗传多效性及其由 sXCI 修饰的不完全外显率，具有 Xq24 微缺失和 sXCI 的女性可能面临生育智障孩子或经历流产的风险。