title: Paucity of genotype-phenotype correlations in STAT3 mutation positive Hyper IgE Syndrome (HIES).
abstract: Autosomal dominant HIES (AD-HIES) is a primary immunodeficiency caused by dominant negative mutations in STAT3 clustered in the DNA binding and SH2 domains. Although in vitro differences in mutational constructs are observed, clinical phenotypic correlates of these genetic changes have not been described. We reviewed the charts of 65 AD-HIES patients (DNA binding n=35; SH2 n=30), recorded the components of the NIH HIES clinical scoring system as well as brain and coronary artery abnormalities and analyzed data by mutation region in adults and children. Patients with SH2 domain mutations had increased frequency of high palate, broad inter-alar distance, upper respiratory tract infections and, in the pediatric sub-group, significant scoliosis. There was suggestion of increased mortality for patients with DNA binding mutations. Although subtle differences in phenotype were observed to depend on the STAT3 genotype, overall the clinical phenotypes were similar between individuals with DNA binding and SH2 domain mutations.
authors.affiliation: Laboratory of Clinical Infectious Diseases, Immunopathogenesis Section, National Institute of Allergy and Infectious Disease/NIH, Bethesda, MD 20892, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Heimall
authors.forename: Joie
authors.initials: J
authors.lastname: Davis
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Shaw
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gu
authors.forename: Pam
authors.initials: P
authors.lastname: Welch
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007589:Job Syndrome / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009154:Mutation; D017434:Protein Structure, Tertiary; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human