De novo myelodysplastic syndrome in a Rothmund-Thomson Syndrome patient with novel pathogenic RECQL4 variants  

作　　者：Chuanhe Jiang Hao Zhang Chuxian Zhao Luxiang Wang Xiaoxia Hu Zengkai Pan 

机构地区：[1]National Research Center for Translational Medicine,State Key Laboratory of Medical Genomics,Shanghai Institute of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Shanghai Zhaxin Traditional Chinese&Western Medicine Hospital,Shanghai 200435,China [3]Collaborative Innovation Center of Hematology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

出　　处：《Blood Science》2023年第2期125-130,共6页血液科学（英文）

基　　金：National Natural Science Foundation of China(grant numbers 81770106,82170206).

摘　　要：Rothmund-Thomson syndrome(RTS)is a rare autosomal-recessive disorder with clinical features consisting of rash,poikiloderma,sparse hair,short stature,juvenile cataracts,skeletal abnormalities,and cancer predisposition.Genetic studies involving detection of pathogenic RECQL4 variants provide the diagnostic certitude.Osteosarcoma was found in two-thirds RECQL4-mutated RTS patients,while hematological malignancies were rarely reported.The variant diversity of RECQL4 gene has not been fully identified and mutations associated with hematologic malignancies are not well described.In this study,we presented a pedigree of RTS from a Chinese family,among which the proband was diagnosed with de novo myelodysplastic syndrome(MDS).Comprehensive medical examination and chromosome karyotyping were performed on the proband.Whole exome sequencing(WES)was performed on the proband,his sister and his mother.The familial cosegregation of sequence variants derived from WES was conducted by polymerase chain reaction–based Sanger sequencing.Structures of candidate RECQL4 mutants were done by in silico analysis to assess pathogenicity.Three novel RECQL4 germline variants,including c.T274C,c.G3014A,and c.G801C,were identified by WES and validated by Sanger sequencing.Prediction of conformation indicated that the structural stability of human RECQL4 protein was largely affected with these variants.The co-occurring U2AF1 p.S34F and TP53 p.Y220C mutations might contribute to the development of MDS.Our study expands the mutational spectrum of RECQL4 and provides underlying molecular mechanism for the development of MDS in RTS patients.

关 键 词：Myelodysplastic Syndrome PEDIGREE RECQL4 Rothmund-Thomson Syndrome Whole Exome Sequencing 

分 类 号：R733.3[医药卫生—肿瘤]