IGLL1 was first reported in relation to autosomal recessive agammaglobulinemia 2 in 1998 (Minegishi Y, et al., 1998, PMID: 9419212). IGLL1 encodes the omega polypeptide chain which associates with the Ig mu chain to form a molecular complex on the surface of pre-B cells. This complex presumably regulates Ig gene rearrangements in the early steps of B-cell differentiation. Biallelic variation in this gene thus results in B cell deficiency and agammaglobulinemia. This gene-disease relationship is supported by both genetic and experimental evidence. Three variants (nonsense, missense, and frameshift) have been reported in five probands (PMIDs: 25502423, 19302039, 27576013, 9419212, and 33178177) and one additional affected family member (PMID: 25502423). A role in disease is supported by the expression of IGLL1 in the relevant tissue of bone marrow, specifically enriched in naïve B-cells (PMID: 2501791) and by an IGLL1 deficient mouse model which recapitulates the block in B cell development seen in patients (PMID: 1591779). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
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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