COMMON VARIABLE IMMUNODEFICIENCY CAUSED BY A HOMOZYGOUS MISSENSE MUTATION IN TRNT1

We identified a 23-year old male patient with mental retardation, dysmorphic features, bilateral cataract, Crohn’s disease, and low levels of IgG, IgA, IgM. He was classified as having common variable immunodeficiency and has been treated with immunoglobulin substitution since the age of 12 months. Initially, the total lymphocyte count, B- and NK-cell numbers were normal but dropped significantly after age 21. Whole exome sequencing identified a homozygous missense mutation (NP_886552.2: exon 3, c. C295T, p. R99W) in the TRNT1 gene. His parents were consanguineous (second cousin marriage) and carried the variant in a heterozygous state, indicating autosomal recessive inheritance.Biallelic mutations in TRNT1 are the cause of sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD) [Chakraborty et al. 2014]. Microcytic hypochromic anemia was demonstrated on some occasions but the patient never required blood transfusions. Expression of the TRNT1 protein was normal in patient skin-derived fibroblasts. Additional investigations into the functional impact of the mutated TRNT1 variant are ongoing.Our case further expands the clinical spectrum associated with TRNT1 mutations. The milder phenotype and longer survival of our patient could possibly be explained by the variants’ location in the less conserved N-terminal region.

Jaar van publicatie:2016