PMC10282741_01
A novel IRF2BP2 mutation in a family with a member diagnosed with IEI. (A) Family tree with a novel heterozygous c.439_450dup mutation in the patient and his father. The proband is indicated by the arrow. Unfilled circle represents unaffected female, and the half-filled square represents unaffected male harboring the IRF2BP2 c.439_450dup variant. (B) Integrative Genomics Viewer (IGV) showing insertion of ACGCCGCAGCCG at position c.450 in exon 1 of IRF2BP2 in the proband and his father, and wild type sequence in his mother. (C) Schematic of the IRF2BP2 protein with an N-terminal Zinc Finger domain, a NLS (nuclear localization signal), and a C-terminal RING domain. The numbers indicate the amino acid positions. The c.439_450dup mutation results in duplication of amino acids (threonine, proline, glutamine, and proline) between position 147 and 150 (denoted by the red arrow). Black arrows indicate mutations of the other three published IRF2BP2 patients.
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f2
His mother, grandparents and other families are unaffected ( Figure 2A ). IRF2BP2 (Mendelian Inheritance in Man (MIM) 615332; NM_182972.2), which was also confirmed in his father ( Figures 2A-C ). It results in duplication of amino acids (threonine, proline, glutamine, and proline) between position 147 and 150 (PM4). This domain was different from previous published IRF2BP2 mutations ( Figure 2C ). The mutation was classified as variant of uncertain significance (VUS) according to the ACMG guidelines based on the following criteria: PM4 (protein length change,  Figure 2C ), PM2 (variant absent from gnomAD database) and PP2 (a novel mutation which may be the probable cause of IEI).