Combined microdeletions and CHD7 mutation causing severe CHARGE/DiGeorge syndrome: clinical presentation and molecular investigation by array-CGH

J Hum Genet. 2010 Nov;55(11):761-3. doi: 10.1038/jhg.2010.95. Epub 2010 Aug 5.

Abstract

Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of CHARGE patients show overlapping phenotypic characteristics with DiGeorge syndrome (thymic hypo/aplasia, hypocalcemia, T-cell immunodeficiency). Very few have been tested or reported to carry a mutation of the CHD7 (chromodomain helicase DNA-binding domain) gene detected in two-thirds of CHARGE patients. In an attempt to explore the genetic background of a severe CHARGE/DiGeorge phenotype, we performed comparative genomic array hybridization in an infant carrier of a CHD7 mutation. The high-resolution comparative genomic array hybridization revealed interesting findings, including a deletion distal to the DiGeorge region and disruptions in other chromosomal regions of genes implicated in immunological and other functions possibly contributing to the patient's severe phenotype and early death.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CHARGE Syndrome* / genetics
  • CHARGE Syndrome* / immunology
  • CHARGE Syndrome* / pathology
  • Comparative Genomic Hybridization / methods*
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • DiGeorge Syndrome* / genetics
  • DiGeorge Syndrome* / immunology
  • DiGeorge Syndrome* / pathology
  • Fatal Outcome
  • Humans
  • Infant
  • Male
  • Mutation / genetics*
  • Phenotype
  • Proteins / genetics
  • Sequence Deletion / genetics*
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / pathology

Substances

  • DNA-Binding Proteins
  • Proteins
  • DNA Helicases
  • CHD7 protein, human