Mutations in the gene encoding transfer RNA (tRNA) nucleotidyltransferase

CCA-adding 1 (TRNT1)

an enzyme essential for the synthesis of the 3′-terminal CCA sequence in tRNA molecules

are associated with a rare syndrome of congenital sideroblastic anemia

B cell immunodeficiency

periodic fevers

and developmental delay (SIFD). Clinical manifestations and immunological phenotypes were assessed in a Chinese patient with novel compound heterozygous mutations in

TRNT1

. The patient required multiple hospitalizations starting at the age of 2 years for recurrent fevers without an infective cause. During the febrile episode

the patient was found to have microcytic hypochromic anemia

B cell lymphopenia

and hypogammaglobulinemia. Targeted gene sequencing identified novel compound heterozygous mutations in the

TRNT1

gene (c.525delT

p.Leu176X; c.938T

>

C

p.Leu313Ser). Immunophenotyping revealed increased CD8

+

T cells

CD4

+

terminally differentiated effector memory helper T lymphocytes (CD4 TEMRA)

and CD4

+

effector memory lymphocytes (CD4 EM). Analysis of CD4

+

T subsets identified decreased T follicular helper cells (Tfh) with a biased phenotype to Th2-like cells. The patient also showed a lower percentage of switched memory B (smB) cells. Additionally

defects in the cytotoxicity of the patient's NK and γδT cells were shown by CD107alpha expression. In conclusion

T

RNT1

mutations may lead to multiple immune abnormality especially humoral and cytotoxicity defects

which indicate that SIFD is not only suffered ‘Predominantly antibody deficiencies’ in IUIS classification system

and further studies are needed to understand the pathogenesis of immunodeficiency in these patients.