Mechanisms of genotype-phenotype correlation in autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency

Abstract

IκBα point mutants accumulate at higher levels compared with truncation mutants and are associated with more severe disease and greater impairment of canonical and noncanonical NF-κB activity in patients with AD EDA-ID.

Immunologic reconstitution following hematopoietic stem cell transplantation despite lymph node paucity in NF-κB–inducing kinase deficiency

“…3,4 Because p100 is under the transcriptional control of the classical NF-kB pathway, activating missense mutations in IkBa disrupt both classical and nonclassical NF-kB signaling pathways. 5 Consequently, lymphorganogenesis is severely impaired, hematopoietic stem cell transplantation (HSCT) fails to achieve immunologic reconstitution, despite excellent donor cell chimerism, and recurrent infections and need for immunoglobulin replacement persist after HSCT. 5 Two homozygous mutations in NIK, NIK pro565Arg , and NIK Val344Met have been described in 3 patients from 2 kindreds, who lacked tonsils and palpable LNs.…”

“…5 Consequently, lymphorganogenesis is severely impaired, hematopoietic stem cell transplantation (HSCT) fails to achieve immunologic reconstitution, despite excellent donor cell chimerism, and recurrent infections and need for immunoglobulin replacement persist after HSCT. 5 Two homozygous mutations in NIK, NIK pro565Arg , and NIK Val344Met have been described in 3 patients from 2 kindreds, who lacked tonsils and palpable LNs. only transplanted patient was reported to be well, but no information on immune function was provided.…”

“…3 Diagnosing peanut allergy involves diagnostic procedures including careful review of clinical reactions, peanut-specific IgE, skin prick test (SPT), and an oral peanut food challenge (FC), optimally performed using a double-blind placebo-controlled FC approach. In addition, component-resolved allergen diagnosis [4][5][6] (CRD) and possibly also peanut conjunctival allergen provocation test 7 (CAPT) may improve peanut allergy diagnosis. Testing CRD in diagnosis of peanut allergy has been found useful in assessing the likelihood of clinical allergy or cross-reactive allergic manifestations.…”

“…Testing CRD in diagnosis of peanut allergy has been found useful in assessing the likelihood of clinical allergy or cross-reactive allergic manifestations. [4][5][6]8,9 The CAPT was recently shown to be feasible and of diagnostic value in peanut allergy 7 and could potentially be…”

Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: A working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma & Immunology

“…76,156 For example, a gene with a proximal nonsense variant might still be expressed by using a downstream alternative start codon, as has been reported in cases of NFKBIA gain-of-function disease. 157 Alternatively, truncated protein products can retain partial function, as evidenced by a variant in CORO1A, encoding the actin-binding protein coronin 1A, which results in hypomorphic combined immunodeficiency rather than SCID. 158 Although variants affecting noncoding regions of the genome cause disease, 159 these types of variants remain a significant challenge for all in silico prediction algorithms because the function of many noncoding regions remains unknown.…”