https://scholars.lib.ntu.edu.tw/handle/123456789/527059
Title: | Clinical features and genetic analysis of Taiwanese patients with the hyper IgM syndrome phenotype | Authors: | Lee W.-I. Huang J.-L. Yeh K.-W. Yang M.-J. Lai M.-C. Chen L.-C. Ou L.-S. Yao T.-C. Lin S.-J. Jaing T.-H. Chen S.-H. Hsieh M.-Y. HSIN-HUI YU YIN-HSIU CHIEN Shyur S.-D. |
Issue Date: | 2013 | Journal Volume: | 32 | Journal Issue: | 9 | Start page/Pages: | 1010-1016 | Source: | Pediatric Infectious Disease Journal | Abstract: | 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 κB essential modulator (NEMO, also known as IKKγ) genes (both X-linked), the CD40, activation-induced cytidine deaminase (AICDA or AID), uracil-DNA glycosylase genes (autosomal recessive) and IκBγ (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. Copyright ? 2013 by Lippincott Williams & Wilkins. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84891629089&doi=10.1097%2fINF.0b013e3182936280&partnerID=40&md5=69efb50b76f0a2085941b41e56123a8c https://scholars.lib.ntu.edu.tw/handle/123456789/527059 |
ISSN: | 0891-3668 | DOI: | 10.1097/INF.0b013e3182936280 | SDG/Keyword: | activation induced cytidine deaminase; CD40 ligand; immunoglobulin; adolescent; amino acid substitution; article; ataxia telangiectasia; autosomal recessive inheritance; binding affinity; cause of death; child; chromosome 1q; chromosome deletion; clinical article; clinical feature; common variable immunodeficiency; controlled study; disease severity; familial disease; female; frameshift mutation; genetic analysis; genetic disorder; human; hyper IgM syndrome; indel mutation; infant; kidney carcinoma; lymphocyte proliferation; male; memory cell; mortality; phenotype; pneumonia; pneumothorax; preschool child; priority journal; school child; sex chromosomal inheritance; Taiwan; CD40 Ligand; Child, Preschool; Female; Humans; Hyper-IgM Immunodeficiency Syndrome; Infant; Male; Mutation; Sequence Deletion; Taiwan |
Appears in Collections: | 醫學系 |
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