Rapid molecular analysis of the STAT3 gene in Job syndrome of hyper-IgE and recurrent infectious diseases.
With the recent discovery of mutations in the STAT3 gene in the majority of patients with classic Hyper-IgE syndrome, it is now possible to make a molecular diagnosis in most of these cases. We have developed a PCR-based high-resolution DNA-melting assay to scan selected exons of the STAT3 gene for mutations responsible for Hyper-IgE syndrome, which is then followed by targeted sequencing. We scanned for mutations in 10 unrelated pedigrees, which include 16 patients with classic Hyper-IgE syndrome. These pedigrees include both sporadic and familial cases and their relatives, and we have found STAT3 mutations in all affected individuals. High-resolution melting analysis allows a single day turn-around time for mutation scanning and targeted sequencing of the STAT3 gene, which will greatly facilitate the rapid diagnosis of the Hyper-IgE syndrome, allowing prompt and appropriate therapy, prophylaxis, improved clinical outcome, and accurate genetic counseling.
Kumánovics
Attila
A
Department of Pathology, Human Genetics, University of Utah School of Medicine and the Associated Regional and University Pathologists Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
Wittwer
Carl T
CT
Pryor
Robert J
RJ
Augustine
Nancy H
NH
Leppert
Mark F
MF
Carey
John C
JC
Ochs
Hans D
HD
Wedgwood
Ralph J
RJ
Faville
Ralph J
RJ
Quie
Paul G
PG
Hill
Harry R
HR
D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons; D005260:Female; D006801:Humans; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D050796:STAT3 Transcription Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human