Jabara et al. (2013) reported 2 sibs, born of consanguineous Lebanese parents, with a primary immunodeficiency characterized by onset in infancy of recurrent bacterial and candidal infections resulting in bronchiectasis and growth delay. Manifestations included mastoiditis, aphthous ulcers, ... Jabara et al. (2013) reported 2 sibs, born of consanguineous Lebanese parents, with a primary immunodeficiency characterized by onset in infancy of recurrent bacterial and candidal infections resulting in bronchiectasis and growth delay. Manifestations included mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis, and meningitis. Organisms included Pseudomonas, Streptococcus, Haemophilus influenza, Klebsiella, and cytomegalovirus, among others. The patients died at ages 7 and 13.5 years. Laboratory studies showed normal levels of absolute lymphocytes and serum immunoglobulins, but specific antibody titers were low despite immunization, and T cells showed impaired proliferative responses to mitogens.
In 2 sibs, born of consanguineous Lebanese parents, with primary immunodeficiency-12, Jabara et al. (2013) identified a homozygous mutation in the MALT1 gene (604860.0001). The mutation, which was found by homozygosity mapping and whole-exome sequencing, segregated with the ... In 2 sibs, born of consanguineous Lebanese parents, with primary immunodeficiency-12, Jabara et al. (2013) identified a homozygous mutation in the MALT1 gene (604860.0001). The mutation, which was found by homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. The mutation was not present in the dbSNP or 1000 Genomes databases, or in 150 ethnically matched controls. Patient T cells showed impaired degradation of the NFKB inhibitor I-kappa-B-alpha (NFKB1A; 164008) and decreased IL2 (147680) expression after T-cell activation, and the mutant cDNA failed to rescue defective activation of T cells from Malt1-null mice, consistent with a loss of function. The clinical and laboratory findings were similar to those of patients with IMD11 (615206), caused by loss-of-function mutations in the CARD11 gene (607210), another member of the CBM complex.