The Research Of Pathogenic Genes Of Klippel-Feil Syndrome Using The Multi-gene Panel Testing

Purposes:Klippel-Feil Syndrome(KFS)is a segmentation malformation of the cervical spine.it is estimated to occur 1 in 40,000 to 42,000 newborns worldwide.KFS manifests as a short neck,a low posterior hairline and limited neck movement resulting from fusion of the cervical spine.But less than 50% of patients have all these three performance at the same time.KFS may associated with other system abnormalities,and congenital diseases.KFS patients with nerve compression symptoms including: nerve root disease,limb paralysis,and even death.KFS cause serious physical and mental problems in patients and bring great burden to the family and society.So,it is essential to explore the early prediction biomarker,diagnostic methods and etiology of therapeutic targets.Since 2010,studies have shown that the etiology of KFS may be associated with gene,environment and developmental abnormalities,especially genetic factors.GDF6,MEOX1,GDF3,MYO18 B and other KFS pathogenic genes have been found all over the world.The aim of this study was to collect blood samples from Chinese KFS patients analyzing the four KFS pathogenic genes: GDF6,MEOX1,GDF3,MYO18 B and five KFS-related genes :CHRNG,PAX1,FLNA,FLNB,FGFR2 in Asian patient by multi-gene Panel analysis.It provides a theoretical basis for predicting the development of disease and guiding clinical early intervention to explore the new and harmful mutations in the whole exon level,and to lay the foundation for in vitro research,animal model experiment and clinical trials.It is also beneficial for KFS individualized early diagnosis and treatment.Methods:19 KFS Patients blood samples collected from January 2010 to December 2016 in department of orthopedics,Peking Union Medical College Hospital.These 19 KFS patients include: 10 males,9 females.These patients are first diagnosed with the maximum age of 45 and the minimum age of 6,and their average age is 14.7 years old.All of the KFS patients were diagnosis by coronal lateral X-ray,neck CT or MRI.The common feature of cervical vertebral body formation or sub-poor fusion caused by deformity.Through the PUBMED,OMIM and other database access to the literature,we independently designed evaluation system for KFS patients and conduct multi-gene Panel analysis.Finally,we also conduct KFS-related gene targeting exon capture probe sequencing.Result:In multi-gene Panel analysis,GDF6,MEOX1,GDF3,and MYO18 B mutation are not occurred in 19 samples.Another two KFS-related genes CHRNG and FLNB mutations are discovered in 2 samples.Conclusion:Previous KFS mutations gene: GDF6,MEOX1,GDF3 and MYO18 B are not found in 19 samples,indicating that these gene mutations could partially explain the occurrence of KFS.CHRNG and FLNB gene mutation are found in two of the samples,which means these two genes mutation have a certain correlation with KFS.It suggests that these two gene mutations may be the cause of KFS...