title: Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: implications for pathogenesis and potential detection by newborn screening.
abstract: Loss of function of DOCK8 is the major cause of autosomal recessive hyper IgE syndrome, a primary immunodeficiency with adaptive and innate immune dysfunction. Patients affected with ARHIES have atopic dermatitis and recurrent, potentially life-threatening viral and bacterial infections. Three consanguineous Pakistani siblings presented with severe atopic dermatitis and superinfection. Direct sequencing of DOCK8 in all three affected siblings demonstrated homozygosity for a deleterious, novel exon 14 frame shift mutation. Current newborn screening for severe combined immunodeficiency syndrome (SCID) and related T cell disorders relies on the quantitation of T Cell Receptor Excision Cells (TRECs) in dried blood spots (DBS). Significantly, both older affected siblings had undetectable TRECs, and TREC copy number was reduced in the youngest sibling. These findings suggest that AR-HIES may be detected by TREC newborn screening, and this diagnosis should be considered in the evaluation of newborns with abnormal TRECs who do not have typical SCID.
authors.affiliation: Department of Pediatrics, University of Kansas Medical Center, Kansas City, USA. mdasouki@kumc.edu
authors.forename: Majed
authors.initials: M
authors.lastname: Dasouki
authors.forename: Kingsley C
authors.initials: KC
authors.lastname: Okonkwo
authors.forename: Abhishek
authors.initials: A
authors.lastname: Ray
authors.forename: Caspian K
authors.initials: CK
authors.lastname: Folmsbeel
authors.forename: Diana
authors.initials: D
authors.lastname: Gozales
authors.forename: Sevgi
authors.initials: S
authors.lastname: Keles
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Puck
authors.forename: Talal
authors.initials: T
authors.lastname: Chatila
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004270:DNA, Circular / Q000097:blood*; D003937:Diagnosis, Differential; D004200:Diseases in Twins; D004485:Eczema / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D015329:Gene Rearrangement, T-Lymphocyte; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007589:Job Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015997:Neonatal Screening / Q000379:methods*; D010154:Pakistan; D010375:Pedigree; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis; D016176:T-Lymphocyte Subsets
chemical_list: D004270:DNA, Circular; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors