Part one:Clinical and molecular analysis of HIES due toDOCK8mutationObjective: To explore the clinical and molecular features of sevenchinese patients with antusomal recessive inherited hyper-lgE syndrome(AR-HIES).Methods: Clinical data peripheral blood, immunological fuctions,lymphocytes classification, of seven patients was analyzed, includingclinical manifestations, etiological examination, imaging stuty. PCR directsequnce analysis of DOCK8gene was performed in10unrelated Chinesefamilies. Most patients suffered from atopic dermatitis, eczema, recurrentskin virus infections, recurrent respiratory tract infections including otitismedia, mastoiditis, nasosinusitis, pneumonia and bronchitis, extremely highserum lgE level, decreaced lgM, and eosinophilia increase.Results: Two homologous deletion and two missense mutations inDOCK8gene were identified in children1-3, which are all new mutations.However,child7showed a wild type and children4,5,6are notquite identified until now becaunse the sequencing have not been finishedwhich may suitable for a new method.Conclusion: Four novel DOCK8mutations are identified in the3cases with HIES. DOCK8gene sequence analysis can confirm thediagnosis. Early diagnosis and jugding the conditions of patients willimprove the outcomes and help to decide whether hematopoietic celltransplantetion are taken in patients. Further researth is needed tounderstand how DOCK8normally function in lymphocytes and howDOCK8deficiency leads to disease. Part two:Novel ELANE Gene Mutation in a Chinese Boywith Severe Congenital NeutropeniaObjective: Severe congenital neutropenia (SCN) is a geneticallyheterogeneous syndrome associated with mutations of ELANE (ELA2),HAX1, GFI1, WAS, CSF3R or G6PC3. Mutation of the ELA2geneencoding human neutrophil elastase is the most common genetic alteration.Accordingly, ELA2genotyping should first be performed for geneticdiagnosis of SCN. Methods: A chinese male pediatric patient was admitted because ofrecurrent respiratory tract infection, digestive tract infection, cervicallymphadenitis with abscess formation, perianal abscess, skin infection andliver abscess. Eventually, he died of bacterial sepsis2month after the liveroperation.His peripheral blood showed a markedly decreased absoluteneutrophil count, and the bone marrow findings revealed early-stagematuration arrest of myelopoiesis. The patient and his parents, elder brotherwere subjected to detection of gene mutation analysis of ELA2by usingPCR based on genomic DNA.Results: Direct DNA sequencing analysis demonstrated that the patientharbored an insertion mutation in exon4of ELA2gene, resulting in5aminoacid insertion into the amino acid sequence(g.795598795599insGGACCAGCTGCCGGC; c.439440insGGACCAGCTGCCGGC; p.134135insAspGlnLeuProAla). But hisparents and elder brother were negative for it.Conclusion: We identified the first Chinese SCN case due to ELA2gene mutation genetically. Maintenance therapy with granulocytecolony-stimulating factor (G-CSF) is standard of care for SCN to prevent theoccurrence of life-threatening bacterial sepsis, but the effect depends on theresponse to G-CSF. In the case of non-responders, stem cell transplantationfrom an HLA-identical sibling is the optimal therapeutic modality. |