Clinical Characteristic Analysis In Adults And Mutant Gene Study In A Family With Hereditary Spherocytosis

Objects:Through the analysis of the clinical characteristics of Chinese adult patients with hereditary spherocytosis and the study of mutant genes in a HS family,to improve the understanding of HS,expand the mutation spectrum of HS in Chinese,and accumulate the genetic counseling data.Methods:The clinical characteristics of 8 adult patients with HS were summarized and analyzed through their general conditions,medical history,clinical manifestations,laboratory examination,complications and treatment outcomes.Whole exome sequencing was used to screen the mutated genes in a clinically diagnosed patient with HS,verify and identify the mutation in family members.Results:Clinical features of HS in adult:（1）Male patients were higher than female patients（male/female=6/2）,with a median age of 27.5 years（15-48 years）.（2）Anemia,jaundice and splenomegaly were the main clinical manifestations of adult patients with HS.（3）Cholelithiasis was a common complication（5/8,63%）.（4）Laboratory examination:mild to moderate anemia,reticulocyte increased in varying degrees;The increase of globular erythrocytes in peripheral blood was relatively low,with only one case（13%）>10%.,the other patients were<10%,and the erythrocyte brittleness test was positive in all.（5）Splenectomy is an effective and reliable treatment for patients with severe hemolytic anemia,high degree of jaundice and splenomegaly,which can relieve the clinical symptoms;（6）Patients with splenectomy will have a sharp rise in blood cells,anti-platelet drugs and inhibit blood cell proliferation treatment should be actively given,to prevent postoperative thrombosis.Mutant gene:（1）There are 13 members in 3 generations in this family,of which 2 have the disease,both male and female;（2）WES and database comparison revealed the heterozygosity deletion of exon 39 of ANK1,base position of 41525784-41526082,transcript of NM₀00037.This mutation is pathogenic,which can cause the defect of erythrocyte membrane protein and cause hemolysis.In addition,a heterozygous missense mutation C.1040 c>T（p.T347I）was detected in the coding region of the exon of SLC22A14 gene in both of the two patients,which is a pathogenic mutation,but no correlation of this gene with HS has been found so far.（3）Quantitative PCR analysis of the exon of the target gene showed that the relative expression of copy number of exon 39 of ANK1 in the diseased member of this family was decreased;None of the non-diseased members carried the mutation.Conclusion:（1）Anemia,jaundice and splenomegaly are common clinical manifestations of HS.The incidence of cholelithiasis in adult HS is higher,and the range of globular erythrocytosis in peripheral blood is relatively low.（2）A heterozygosity deletion mutation in exon 39 of ANK1 gene（chr8:41525784-41526082）was found in this family.This mutation has not been reported yet,and may be a new pathogenic mutation of HS.（3）A heterozygous missense mutation c.1040 c>T（p.T347I）was detected in the exon coding region of SLC22A14 gene in the preexisting patient and her disaffected fathers,its pathogenicity and correlation with HS could not be determined yet.