Novel biallelic TRNT1 mutations lead to atypical SIFD and multiple immune defects

Mutations in the gene encoding transfer RNA(tRNA)nucleotidyltransferase,CCAadding 1(TRNT1),an enzyme essential for the synthesis of the 30-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 andγτT cells were shown by CD107alpha expression.In conclusion,TRNT1 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.

Corrigendum to “Novel biallelic TRNT1 mutations lead to atypical SIFD and multiple immune defects” [Genes Dis 7 (1) (2020) 128-137]

We regret that an error was made in“Novel biallelic TRNT1 mutations lead to atypical SIFD and multiple immune defects”(Volume 7,Issue 1,March 2020,Pages 128e137).In the original manuscript,the grant number of the Natural Science Foundation of China was incorrectly written with the project number.The correct grant number is 81601753.We apologize for the error and for any inconvenience that may cause to the readers and the editors of this journal.

Phenotypic characterization of patients with activated PI3Kδ syndrome 1 presenting with features of systemic lupus erythematosus

Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with APDS1.In this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)phenotype.The clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of SLE.The immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch recombination.These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE.Meanwhile,we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1.The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE phenotype.The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy.Here,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.