Clinical features and genetic analysis of Taiwanese patients with the hyper IgM syndrome phenotype
Journal
Pediatric Infectious Disease Journal
Journal Volume
32
Journal Issue
9
Pages
1010-1016
Date Issued
2013
Author(s)
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.
Shyur S.-D.
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.
SDGs
Other Subjects
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
Type
journal article