title: Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.
abstract: More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are associated with T-B + NK + SCID phenotype. Severe immunodeficiency with CHARGE syndrome has been noted only rarely Omenn syndrome is a rare autosomal recessive form of SCID with erythroderma, hepatosplenomegaly, lymphadenopathy and alopecia. Hypomorphic recombination activating genes 1 and 2 mutations were first described in patients with Omenn syndrome. More recently, defects in Artemis, RMRP, IL7Ralpha and common gamma chain genes have been described. We describe four patients with mutations in CHD7, who had clinical features of CHARGE syndrome and who had T-B + NK + SCID (two patients) or clinical features consistent with Omenn syndrome (two patients). Immunodeficiency in patients with DiGeorge syndrome is well recognized--CHARGE syndrome should now be added to the causes of T-B + NK + SCID, and mutations in the CHD7 gene may be associated with Omenn-like syndrome.
authors.affiliation: Department of Paediatric Immunology, Newcastle upon Tyne Hospitals Foundation Trust, Newcastle upon Tyne, UK. a.r.gennery@ncl.ac.uk
authors.forename: A R
authors.initials: AR
authors.lastname: Gennery
authors.forename: M A
authors.initials: MA
authors.lastname: Slatter
authors.forename: J
authors.initials: J
authors.lastname: Rice
authors.forename: L H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: D
authors.initials: D
authors.lastname: Barge
authors.forename: A
authors.initials: A
authors.lastname: McLean-Tooke
authors.forename: T
authors.initials: T
authors.lastname: Montgomery
authors.forename: J A
authors.initials: JA
authors.lastname: Goodship
authors.forename: A D
authors.initials: AD
authors.lastname: Burt
authors.forename: T J
authors.initials: TJ
authors.lastname: Flood
authors.forename: M
authors.initials: M
authors.lastname: Abinun
authors.forename: A J
authors.initials: AJ
authors.lastname: Cant
authors.forename: D
authors.initials: D
authors.lastname: Johnson
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D009154:Mutation; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000002:abnormalities
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human