FERMT3 was first reported in relation to autosomal recessive leukocyte adhesion deficiency 3 in 2008 (Mory et al., PMID: 18779414). At least 15 unique variants (primarily nonsense, along with other LoF splicing and frameshift variants, and few inactivating missense variants) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 18 probands in 6 publications (PMIDs: 18779414, 19234463, 19234460, 19064721, 21441448, 22139635). Variants in this gene segregated with disease in two additional family members. More evidence is available in the literature, but the maximum score for genetic and experimental evidence has been reached. This gene-disease relationship is supported by the enhanced expression of FERMT3 in hematopoietic tissues, its biochemical function in integrin activation which is altered in patient cells but can be rescued, and a null mouse model which recapitulates both cellular defects and clinical phenotypes observed in human LAD-III patients. In summary, FERMT3 is definitively associated with autosomal recessive leukocyte adhesion deficiency 3. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
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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