Whole exome gene sequencing report of 3 cases of hereditary spherocytosis
Objective:To investigate the molecular pathogenesis,clinical manifestations and therapeutic management of hereditary spherocytosis(HS)and the value of whole exome sequencing(WES).Methods:WES technology was used to detect genetic variants in suspected HS patients,and variants were evaluated for pathogenicity according to the American College of Medical Genetics and Genomics(ACMG)guideline.The latest literature related to HS was reviewed to provide a systematic review of the molecular mechanisms,clinical phenotypes and therapeutic management.Results:Clinical manifes-tations(anemia,jaundice,splenomegaly)and major laboratory test results(e.g.,markedly increased spherical red blood cells seen in peripheral blood smears)of the 3 patients were consistent with typical HS features,and mutations in the SLC4A1(p.R808H),SPTB(p.Y1606*),and SPTA1(p.L2380R)genes were detected by WES,respectively,and Sanger sequencing validation using exfoliated buccal mucosal cells confirmed that all of them were germline heterozygous mutations,and the 3 mutations were classified as pathogenic mutations according to the ACMG guideline.Additionally,the SPTB(p.Y1606*)and SPTA1(p.L2380R)mutations were newly discovered pathogenic mutations,which expanded the pathogenic mutation spectrum of the related genes.Conclusion:WES can identify novel pathogenic mutations and play an important role in molecular diagnosis,therapeutic management and genetic counseling of HS.
NETL
NSTL
万方数据
