title: X-linked hyper IgM syndrome: clinical, immunological and molecular features in patients from India.
abstract: BACKGROUND
  X-linked hyper-IgM (XHIM) is a primary immunodeficiency disorder characterized by recurrent infections, low serum IgG and IgA and normal or elevated IgM. It results from mutations in the CD40 ligand (CD40L) gene. Confirmation of diagnosis with identification of underlying molecular defect is important for the initiation of appropriate therapeutic interventions, including immunoglobulin replacement, antibiotics and bone marrow transplantation.
  
  
  METHODS
  To investigate the molecular basis of XHIM, we evaluated 7 patients with suspected XHIM and abnormal CD40L expression on activated CD4(+) T lymphocytes. The entire coding region and intronic splice sites of the CD40L gene were sequenced from the genomic DNA of the patients.
  
  
  RESULTS
  7 mutations; 3 nonsense (c.172delA, c.A229T, c.C478T), 1 missense (c.A506G) and 3 splice sites [c.346+2(T→C), c.289-1(G→C), c.346+1(G→T)] were identified, out of which 5 were novel.
  
  
  CONCLUSIONS
  A wide heterogeneity in the nature of mutations has been observed in Indian XHIM patients in the present study. Identification of mutations in this rare disorder will help in genetic diagnosis in affected families which could be further useful in prenatal diagnosis.
authors.affiliation: National Institute of Immunohaematology, KEM Hospital, 13th Floor, Parel, Mumbai 400012, India. Electronic address: madkaikarm@icmr.org.in.
authors.forename: Manisha
authors.initials: M
authors.lastname: Madkaikar
authors.affiliation: National Institute of Immunohaematology, KEM Hospital, 13th Floor, Parel, Mumbai 400012, India.
authors.forename: Maya
authors.initials: M
authors.lastname: Gupta
authors.affiliation: National Institute of Immunohaematology, KEM Hospital, 13th Floor, Parel, Mumbai 400012, India.
authors.forename: Sushant
authors.initials: S
authors.lastname: Chavan
authors.affiliation: National Institute of Immunohaematology, KEM Hospital, 13th Floor, Parel, Mumbai 400012, India.
authors.forename: Khushnooma
authors.initials: K
authors.lastname: Italia
authors.affiliation: Department of Immunology, Wadia Hospital, Parel, Mumbai 400012, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Desai
authors.affiliation: Nanavati Hospital, Mumbai 400056, India.
authors.forename: Rashid
authors.initials: R
authors.lastname: Merchant
authors.affiliation: Ganga Ram Hospital, Delhi 110060, India.
authors.forename: Nita
authors.initials: N
authors.lastname: Radhakrishnan
authors.affiliation: National Institute of Immunohaematology, KEM Hospital, 13th Floor, Parel, Mumbai 400012, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D015870:Gene Expression; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000175:diagnosis* / Q000209:etiology*; D016130:Immunophenotyping; D007194:India; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D023201:CD40 Ligand
keywords: CD154; CD40L; CD40L gene; T-cell and B-cell immunodeficiency; X-linked hyper-IgM syndrome (XHIM)