Preliminary Study On The Significance Of Bone Marrow Failure Gene In The Bone Marrow Failure Syndromes In Children

Objective:Using the next generation sequencing technology to analyse related bone marrow failure genes,and combining with the clinical characteristic,to discuss the significance.of bone marrow failure gene in bone marrow failure syndromes in children.Method:Choose 89 cases of suspected bone marrow failure syndromes from September 2014 to November 2016 in our hospital as the research object,collect their clinical data and extract their peripheral blood DNA.Break it up and amplify PCR,so as to establish the whole genomic library with target genes,and then capture genes related hematological genetic diseases by the liquid Capture Kit,using a new generation sequencing Illumina HiSeq 2500 to analyse bioinformation after high-throughput sequencing.In the end,find out all the related gene mutation information in these samples and verify their pedigree.Results: 1?After next generation sequencing 89 suspected bone marrow failure syndrome children,,78 cases of them are diagnosed of bone marrow failure syndromes.9 cases are disgnosed of inherited bone marrow failure syndromes,including 7 cases of fanconi anemia?FA?,1 case of congenital dyskeratosis?DC?,1 case of congenital neutropenia?CN?;69 cases of them are diagnosed of acquired bone marrow failure syndromes,including 5 cases of myelodysplastic syndrome?MDS?,64 cases of acquired aplastic anemia?AAA?.The rest 11 cases are granulocytopenia affected by viral or bacterial.12 cases?9 IBMFS and 3 MDS?,accounting for 15% of BMFS are sequenced by pathogenic genetic mutations.2?7 cases of FA,5 of them had been diagnosed of aplastic anemia or immune thrombocytopenic purpura.2/5 FA's MMC test were positive,1/5 FA's SCGE test was positive.All of then are sequenced by pathogenic genetic mutations,6 of them are FANCA mutations,1 case are FANCD1?BRCA2?mutation.We find 1 exon deletion and 12 mutation sites.The deletion of exon 23-30:and mutation sites in the FANCA gene: c.2994T>G,c.1811₁812del,c.G4195 A,c.3973 delG,c.3270₃271del,c.2749C>T,c.1889A>T,the mutation sites in the FANCD1?BRCA2?mutation sites:c.T943 A,c.T7469 C,are all new discovered.3?1 case of DC with a preliminary misdiagnosis of aplastic anemia in the past two years,eventually disgnosed by the genetic screening TINF2 gene mutation:c.844 c > T.4?1 case of SCN child with recurrent oral infections for more than four year,was disgnosed by genetic screening.ELANE gene mutation: c.377 c > T.5?In 5 cases of MDS,3 of them were screened out gene mutation.Mutation site in the GATA2 gene: c.1081C>T,has been reported;mutation site in the TET2 gene: c.C2233 T,and mutation site in the MPL,c.981-1G>C mutations,are all new discovered.6?In 64 cases of acquired AA children,49 cases?acounting for 76 percent?carry with unclear and different likelypathogenic mutation sites,detected 111 unclear likeypathogenic mutation sites.Conclusion: 1?Applying the next generation sequencing bone marrow failure gene to patients with suspected bone marrow failure syndromes can quickly provide accurate basis for the diagnosis and avoid misdiagnosis.It is a suggestion that we should apply the next generation sequencing in all children with suspected bone marrow failure syndromes.2?The new mutation of bone marrow failure gene can enrich the gene profile of the disease,However,the role of the bone marrow failure syndrome in the pathogenesis of bone marrow failure remains to be further investigated.