RESUMO
BACKGROUND AND OBJECTIVES: Next generation sequencing (NGS) has promising applications in transfusion medicine. Exome sequencing (ES) is increasingly used in the clinical setting, and blood group interpretation is an additional value that could be extracted from existing data sets. We provide the first release of an open-source software tailored for this purpose and describe its validation with three blood group systems. MATERIALS AND METHODS: The DTM-Tools algorithm was designed and used to analyse 1018 ES NGS files from the ClinSeq® cohort. Predictions were correlated with serology for 5 antigens in a subset of 108 blood samples. Discrepancies were investigated with alternative phenotyping and genotyping methods, including a long-read NGS platform. RESULTS: Of 116 genomic variants queried, those corresponding to 18 known KEL, FY and JK alleles were identified in this cohort. 596 additional exonic variants were identified KEL, ACKR1 and SLC14A1, including 58 predicted frameshifts. Software predictions were validated by serology in 108 participants; one case in the FY blood group and three cases in the JK blood group were discrepant. Investigation revealed that these discrepancies resulted from (1) clerical error, (2) serologic failure to detect weak antigenic expression and (3) a frameshift variant absent in blood group databases. CONCLUSION: DTM-Tools can be employed for rapid Kell, Duffy and Kidd blood group antigen prediction from existing ES data sets; for discrepancies detected in the validation data set, software predictions proved accurate. DTM-Tools is open-source and in continuous development.
Assuntos
Alelos , Antígenos de Grupos Sanguíneos/análise , Antígenos de Grupos Sanguíneos/genética , Sequenciamento do Exoma/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Software , Sistema do Grupo Sanguíneo Duffy/genética , Variação Genética , Técnicas de Genotipagem , Humanos , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Metaloendopeptidases/genética , Receptores de Superfície Celular/genética , Transportadores de UreiaRESUMO
A 19 year old otherwise healthy male presented with a history of acute onset left neck pain with subsequent swelling and development of a left neck mass that progressively enlarged over a two month period. Imaging studies revealed a solid heterogeneous mass with prominent calcifications displacing normal structures. The lesion was resected via transcervical approach and a diagnosis of calcifying fibrous tumor (CFT) was rendered. The clinical, radiographic, histologic and immunophenotypic features of CFT are discussed. CFT is a rare benign soft tissue tumor with distinctive histologic findings. They present as well-circumscribed but unencapsulated, paucicellular lesions consisting of hyalinized fibrous tissue with chronic lymphoplasmacytic inflammation and variable amounts of both psammomatous and dystrophic calcifications distributed throughout. They are found in numerous locations throughout the body, most often in the gastrointestinal tract or subcutaneous soft tissue, but are relatively uncommon in the neck. This article describes a case of CFT which presented as an enlarging neck mass in a young male.