A Case Of Phytosterolemia Family, Genetic Research And Literature Review

Objective:To explore the clinical manifestations,molecular biological characteristics and treatment options of 1 cases of phytosteroemia family and its gene pathogenesis,and to identify the related diseases of blood system including anemia and macrothrombocytopenia.Methods :The proband is a 52-year-old male,presented with anemia,thrombocytopenia,splenomegaly,liver function damage and xanthoma.There were 8 brothers and sisters.There were 3 family members with history of anemia,thrombocytopenia and splenomegaly,A total of 6 family members including probands were collected this time,and the morphology of the peripheral blood red blood cells and platelets of the probands and their family members was observed using an optical microscope.Amplify all exons and flanking sequences of ABCG5 and ABCG8 genes of proband’s genomic DNA by PCR,the PCR products were sequenced by Sanger sequencing method.According to the mutation sites of probands,PCR amplification and sequencing of the corresponding fragments were performed on the five family members.By searching relevant keywords such as phytosterolemia and sitosterolemia in Wanfang database and China HowNet,Search related keywords such as ABCG5,ABCG8,mutation,phytosterolemia mutation,sitosterolemia mutation in Pubmed,Retrieving literatures on gene mutations related to phytosteroemia,analysis and summary of ABCG5 and ABCG8 pathogenic gene mutations.Results:Huge platelets and mouth-shaped red blood cells can be seen in the peripheral blood smear of the proband,2 similar cases were found among the family members.Several mutations were found in the gene of ABCG5 and ABCG8 gene of proband and the family members.Two nonsense mutations(c.64C>T,p.Q22 X and c.1336C>T,p.R446X)and one missense mutation(c.1810C>G,p.Q60E)were found in ABCG5 gene.-19 T>G mutation before ATG,two missense mutations(c.161A> G,p.Y54 C and c.1895 T>C,p.V632A)and g.12902 T>C mutation in the intron between exon 3 and 4 were found in the ABCG8 gene.Exon 1 c.64C> T(p.Q22X)and exon 10 c.1336C> T(p.R446X)of ABCG5 gene in this family are pathogenic mutations,which are derived from different alleles,while others Gene mutations are non-pathogenic polymorphic sites.Through database search,a total of 54 pathogenic mutations of ABCG5 gene and 67 pathogenic mutations of ABCG8 gene were collected.Among the pathogenic mutations of ABCG5 gene,there are 20 missense mutations(37.0%),12 splice mutations(22.2%),11 frameshift mutations(20.4%),10 nonsense mutations(18.5%),1 non-coding region mutation(1.9%);ABCG8 gene pathogenic mutation,including 28 missense mutations(41.8%),frameshift mutations in 20 cases(29.9%),nonsense mutations in 12 cases(17.9%),splice mutations 7 cases(10.4%).Conclusions:The compound heterozygous mutations c.64C> T(p.Q22X)and c.1336C> T(p.R446X)in the ABCG5 gene are the genetic pathogenesis of this phytsterolemia family.