M232 VARIABLE PHENOTYPES ASSOCIATED WITH P.H648TFSX20 PATHOGENIC VARIANT IN CARMIL2 GENE: A REPORT OF TWO CASES

Abstract

Biallelic pathogenic variants in CARMIL2 (capping protein regulator and myosin 1 linker 2) cause combined immune deficiency. A newly described pathogenic variant, c.1942delC (p.H648TfsX20), results in a premature stop codon, disrupting the ability of CARMIL2 protein to link CD28 with proximal effectors, needed for T cell activation and differentiation. Here, we report two Mexican girls with homozygous c.1942delC variant in CARMIL2, but who presented with differing clinical manifestations, demonstrating significant clinical variability associated with CARMIL2 defects even in individuals with the same genotype.