Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia with immunodeficiency

Blood. 2012 Jun 7;119(23):5458-66. doi: 10.1182/blood-2011-05-354167. Epub 2012 Apr 19.

Abstract

Somatic mosaicism has been described in several primary immunodeficiency diseases and causes modified phenotypes in affected patients. X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the NF-κB essential modulator (NEMO) gene and manifests clinically in various ways. We have previously reported a case of XL-EDA-ID with somatic mosaicism caused by a duplication mutation of the NEMO gene, but the frequency of somatic mosaicism of NEMO and its clinical impact on XL-EDA-ID is not fully understood. In this study, somatic mosaicism of NEMO was evaluated in XL-EDA-ID patients in Japan. Cells expressing wild-type NEMO, most of which were derived from the T-cell lineage, were detected in 9 of 10 XL-EDA-ID patients. These data indicate that the frequency of somatic mosaicism of NEMO is high in XL-ED-ID patients and that the presence of somatic mosaicism of NEMO could have an impact on the diagnosis and treatment of XL-ED-ID patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Cell Proliferation
  • Child, Preschool
  • Ectodermal Dysplasia 1, Anhidrotic / complications*
  • Ectodermal Dysplasia 1, Anhidrotic / genetics*
  • Ectodermal Dysplasia 1, Anhidrotic / immunology
  • Humans
  • I-kappa B Kinase / genetics*
  • Immunologic Deficiency Syndromes / complications*
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology
  • Infant
  • Infant, Newborn
  • Mosaicism*
  • Phenotype
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • IKBKG protein, human
  • I-kappa B Kinase