Gene Heterogenicity Diagnosis on Children with Complicated Immunological and Hematological Abnormalities

Some abnormalities in peripheral blood of children coexist with abnormal immunological function,such as autoantibodies, humoral and /or cellular immunity disorders.It is difficult to diagnose in the past,especially in children suspected withImmune Thrombocytopenia and Evans syndrome.

To explore accurate diagnostic method in children with complicated immunological and hematological abnormalities, 9 complicated cases with positive findings under 14 years old were studied. Gene mutations were screened with high-throughput sequencing, genetic data were analyzed using bioinformatics and clinical information analysis technology and the suspected pathogenic mutation were verified using Sanger sequencing technology. Interpretation of pathogenic mutation included biological significance, genetic significance and coincidence degree of clinical characteristics. In suspected cases , proband , parents and germline cells were examined as well.

The initial diagnosis were: 3 cases of Immune Thrombocytopenia (the third was thalassemia with secondary ITP after hematopoietic stem cell transplantation), 4 cases of Evans syndrome, 1 EB virus-related Hemophagocytic syndrome , 1 case of unexplained hemolytic anemia and neutropenia. The main abnormal genes found were as follows respectively: WAS, MYH9, GP1BA,NF1+CBL, ITGA2,VWF, ABCG8, ERCC4,RPS19+LRBA.In the end ,they were diagnosed sequentially as Wiskott-Aldrich syndrome, Epstein syndrome/Fechtner syndrome/ Hemorrhagic disease platelet type 6, Von Willebrand disease/ Hemorrhagic disease platelet type 3, Juvenile Myelomonocytic Leukemia, Glycoprotein Ia deficiency / Hemorrhagic disease platelet type 6, II type Von Willebrand disease, Sitosterolemia, Fanconi anemia complementation group Q, Diamond-Blackfan anemia/Common variant immunodeficiency disease type 8.

With multi-factor comprehensive analysis including the effect of mutation, mode of inheritance and clinical characteristics, mutations can be verified as causative agents.If gene sequencing of only hematological system diseases can not explain, it is suggested to do the whole exon mutation analysis of single gene genetic disease or CNVseq, mtDNAseq if necessary. Complex genetic defects exist in some complicated immunological and hematological abnormalities