FAAP24 was reported in relation to autosomal recessive lymphoproliferative syndrome in 2016 (Daschkey et al., PMID: 27473539). In this study, a homozygous missense variant in FAAP24 was identified in two siblings from a consanguineous family with a fatal Epstein-Barr virus (EBV)-related lymphoproliferative disease. The allele frequency in the general population for the variant in these cases is higher than would be expected for disease-causing variants in this gene and was flagged as contradictory evidence. Given the allele frequency of the variant (particularly the presence of multiple homozygotes past the age of onset in the general population) in the only two patients with this disorder reported to date, there is convincing evidence disputing the relationship between FAAP24 and autosomal recessive lymphoproliferative syndrome.
This gene-disease association may be supported by in vitro functional assays. Experimental evidence assessing FAAP24 expression and biochemical function supported this gene’s role in DNA damage repair pathways (PMID: 27473539, 23999858, 23333308). However, it is currently unclear if this role is consistent with the mechanism of disease and the data was insufficient for scoring.
In summary, the evidence supporting the relationship between FAAP24 and autosomal recessive lymphoproliferative syndrome has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role FAAP24 plays in this disease.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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