Anhidrotic Ectodermal Dysplasia with ImmunoDeficiency (EDA-ID, OMIM 300291) and Incontinentia Pigmenti (IP, OMIM 308300) are two rare diseases, caused by mutations of the IKBKG/NEMO gene. The protein NEMO/IKKγ is essential for the NF-κB activation pathway, involved in a variety of physiological and cellular processes, such as immunity, inflammation, cell proliferation, and survival. A wide spectrum of IKBKG/NEMO mutations have been identified so far, and, on the basis of their effect on NF-κB activation, they are considered hypomorphic or amorphic (loss of function) mutations. IKBKG/NEMO hypomorphic mutations, reducing but not abolishing NF-κB activation, have been identified in EDA-ID and IP patients. Instead, the amorphic mutations, abolishing NF-κB activation by complete IKBKG/NEMO gene silencing, cause only IP. Here, we present an overview of IKBKG/NEMO mutations in EDA-ID and IP patients and describe similarities and differences between the clinical/immunophenotypic and genetic aspects, highlighting any T and B lymphocyte defect, and paying particular attention to the cellular and molecular defects that underlie the pathogenesis of both diseases.

中文翻译：

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EDA-ID和IP，是同一枚硬币的两个面孔：相同的IKBKG / NEMO突变影响NF-κB途径如何导致免疫缺陷和/或炎症。

具有免疫缺陷的无软骨变性表皮发育不良（EDA-ID，OMIM 300291）和色素失禁（IP，OMIM 308300）是两种罕见的疾病，是由IKBKG / NEMO基因突变引起的。NEMO /IKKγ蛋白对于NF-κB激活途径至关重要，涉及多种生理和细胞过程，例如免疫，炎症，细胞增殖和存活。迄今为止，已经发现了各种各样的IKBKG / NEMO突变，根据它们对NF-κB激活的影响，它们被认为是亚型或无定型（功能丧失）突变。已经在EDA-ID和IP患者中鉴定了IKBKG / NEMO亚型突变，该突变降低但不消除NF-κB活化。取而代之的是，通过完全的IKBKG / NEMO基因沉默消除了NF-κB活化的无定形突变仅引起IP。这里，