Clinical Phenotype Analysis And Molecular Diagnostics Research Of Congenital Central Hypoventilation Syndrome

ObjectiveClinical diagnostic criteria of congenital central hypoventilation syndrome establishedby consensus in1993, has been always adopted, CCHS is a rare genetic disease, belongsto autosomal dominant, PHOX2B mutations located in the4p12is considered to be thegenetic basis for CCHS.The main clinical manifestations show chronic respiratoryfailure, are not associated with significant pulmonary disease, heart disease, respiratorytract malformations, diaphragmatic elevation, neuromuscular disease and so on, A seriesof primary disease. adequate spontaneous ventilation is the typical clinical featureswhile awake, Sleep needs mechanical ventilation due to lack of spontaneous ventilation,prone to hypercapnia, even accompanied by hypoxemia; The sicker children are eitherawake or sleep requiring mechanical ventilation due to lack of spontaneous ventilation.The mutations of the majority of children sufferred from CCHS belong to of newmutation heterozygotes, PHOX2B mutation mosaic are carried by the parents ofchildren Approximately5%. At present, the research data shows that extensionmutation of polyalanine of PHOX2B is stable In the period of meiosis, Parental carriedthe mutated gene will be passed on to offspring stably.there are differences between information collected from our hospital and this criteria.The severity of the onset of CCHS’children are related with clinical phenotypecharateristic and the presence of comorbidities and the types of mutations. This group ofresearchers has been benetited for screening earlier and making further moleculargenomic for appropriate patients.due to the different types of mutations and Pathogenesis. there are differences among the clinical symptoms and genetic risk andprognosis.At present, gene sequencing and gene fragment analysis have been usedclinically to detect. and determined PHOX2B gene mutation, And analysised the geneticmechanisms, clinical characteristics and type of disease-causing mutations, Toinvestigate the pathogenesis of the molecular genetics, And reviewed the literaturerelated.Mothods1.Apply retrospective analysis. The information from ten CCHS neonates that had beendefinitly diagnosed with molecular study from2008to2013were collected. For eachpatient, the presence or absence of the major Clinical features, minor features listed inthe published diagnostic criteria that provided by Mellins was recorded. Then, analysedthe typically clinical features of Chinese neonates with CCHS.2. Take the peripheral blood of the children,Extracting DNA, amplifying PHOX2B gene1-3exons by methylation specific PCR.And the product is used to detected the genesequence analysis.Results10cases of children are with the following clinical features: they are lowhypoventilation In sleep and need mechanical ventilation, Detection of blood has beenprompted hypercapnia, CO2partial pressure consistently higher than60mmHg duringsleep,10cases of children were all performed molecular genetic testing, and confirmedthat the causative gene is PHOX2B, Combined with the related literature, they can bediagnosed with CCHS.PHOX2B gene sequencing analysis reveals that the DNAcopynumber variation of the first three exons of the Pathogenic gene PHOX2B of10cases ofchildren lead to different increase in the number of alanine.Conclusions1. The ventilation is normal, When the children are awake,and slow shallow breathingduring sleep, and with Hypercapnia,is a major clinical manifestations of CCHS, requiring mechanical ventilation support.2. The molecular etiology of10cases of children is the PHOX2B gene coding alanineof exon3of expansion mutations. The analysis of Gene mutation is an effective andproven diagnostic method for detecting the CCHS.