期刊
PEDIATRIC INFECTIOUS DISEASE JOURNAL
卷 32, 期 9, 页码 1010-1016出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/INF.0b013e3182936280
关键词
hyper IgM syndrome (HIGM); activation-induced cytidine deaminase (AICDA or AID); CD40; CD40 ligand (CD40L); uracil-DNA glycosylase (UNG); nuclear factor kappa B essential modulator gene (NEMO); I kappa B alpha (IKBA); ataxia-telangiectasia mutation (ATM); Bruton's tyrosine kinase (Btk); SLAM-associated protein/SH2 domain 1A (SAP /SH2DA1)
资金
- Chang Gung Medical Research Progress Grant [CMRPG 32069, 450021, 490011]
- National Science Council [NSC99-2314-B-182-003-MY3, NMRPD190315]
Objectives: Hyper IgM syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, defective class switch recombination and somatic hypermutation, are heterogeneous disorders with at least 6 distinct molecular defects, including the CD40 ligand (CD40L) and the nuclear factor kappa B essential modulator (NEMO, also known as IKK gamma) genes (both X-linked), the CD40, activation-induced cytidine deaminase (AICDA or AID), uracil-DNA glycosylase genes (autosomal recessive) and I kappa B alpha (IKBA) (autosomal dominant). Our objective was to determine the molecular basis and clinical features of Taiwanese patients with the HIGM phenotype. Methods: Clinical manifestations and candidate genes were analyzed in a nationwide population-based study. Results: Among 14 patients (12 unrelated families) since 2003, 10 patents were identified (8 families) with CD40L mutations, including 2 novel deletions of A nucleotide (Del 347A and Del 366A), both frameshift and stop at the 127th location; 1 novel AID deletion mutation lack of the 37thAsp and 38th Ser; 1 ataxia-telangiectasia mutation; and 1 deletion of chromosome 1q42. An adult-onset patient with mutant (Thr254Met)CD40L had approximately 30% detectable affinity and therefore less severity. Memory B cells decreased in patients with CD40L and activation-induced cytidine deaminase mutations. Three mortalities encompassed renal cell carcinoma in 1 patient with (Tyr169Asn)CD40L, pneumothorax in 1 with (Tyr140Stop) CD40L and pneumonia after chemotherapy in an ataxia-telangiectasia patient. One patient without detectable genetic defects but normal lymphocyte proliferation resembled the mild form of common variable immune deficiency phenotype. Conclusions: In contrast to those with AICDA mutation, small chromosome 1 q42 deletion and unknown genetic defect, the majority (10/14; 71.4%) with CD40L mutations except (Thr254Met) and an ataxia-telangiectasia patient had the severe form of HIGM phenotype.
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