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Reassessment of the NF1 variants of unknown significance found during the 20-year activity of a genetics diagnostic laboratory.
Martorana, Davide; Barili, Valeria; Uliana, Vera; Ambrosini, Enrico; Riva, Matteo; De Sensi, Erika; Luppi, Elena; Messina, Corinne; Caleffi, Edoardo; Pisani, Francesco; Percesepe, Antonio.
Afiliación
  • Martorana D; Medical Genetics, University Hospital of Parma, 43126, Parma, Italy; CoreLAB Research Center, University Hospital of Parma, 43126, Italy.
  • Barili V; Medical Genetics, Department of Medicine and Surgery, University of Parma, Parma, Italy.
  • Uliana V; Medical Genetics, University Hospital of Parma, 43126, Parma, Italy.
  • Ambrosini E; Medical Genetics, University Hospital of Parma, 43126, Parma, Italy.
  • Riva M; Medical Genetics, Department of Medicine and Surgery, University of Parma, Parma, Italy.
  • De Sensi E; Medical Genetics, Department of Medicine and Surgery, University of Parma, Parma, Italy.
  • Luppi E; Medical Genetics, University of Bologna, Italy.
  • Messina C; Medical Genetics, University Hospital of Parma, 43126, Parma, Italy.
  • Caleffi E; Plastic Surgery, University Hospital of Parma, 43126, Parma, Italy.
  • Pisani F; Children's Neuropsychological Services, Department of Medicine and Surgery, University of Parma, Parma, Italy.
  • Percesepe A; Medical Genetics, University Hospital of Parma, 43126, Parma, Italy; Medical Genetics, Department of Medicine and Surgery, University of Parma, Parma, Italy. Electronic address: antonio.percesepe@unipr.it.
Eur J Med Genet ; 66(11): 104847, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37751797
The finding of variants of uncertain significance (VUS) in the activity of a diagnostic genetic laboratory is a common issue, which is however provisional and needs to be periodically re-evaluated, due to the continuous advancements in our knowledge of the genetic diseases. Neurofibromatosis type 1, caused by the occurrence of heterozygous pathogenic NF1 variants, is a good model for studying the evolution of VUS, due to the widespread use of genetic testing for the disease, the constant enrichment of the international databases with NF1 variants and the full adult penetrance of the disease, which makes genotyping the parents a crucial step in the diagnostic workflow. The present study retrospectively reviewed and reinterpreted the genetic test results of NF1 in a diagnostic genetic laboratory in the period from January 1, 2000 to December 31, 2020. All the VUS were reinterpreted using the 2015 consensus standards and guidelines for the interpretation. Out of 589 NF1 genetic tests which were performed in the period, a total of 85 VUS were found and reinterpreted in 72 cases (84.7%): 21 (29.2%) were reclassified as benign/likely benign, whereas 51 (70.8%) were recoded as pathogenic/likely pathogenic with a significant trend distribution (Chi square test for trend p = 0.005). Synonymous VUS have mainly been reclassified as class 1 and 2 (7/8, 87.5%), whereas missense variants have been attributed to class 4 and 5 in 38 out of the 58 cases (65.5%). These findings underline an improvement in the classification of variants over time, suggesting that a reinterpretation of the genetic tests should be routinely performed to support the physicians in the clinical diagnosis of genetic diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurofibromatosis 1 / Predisposición Genética a la Enfermedad Tipo de estudio: Diagnostic_studies / Guideline / Prognostic_studies Límite: Adult / Humans Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurofibromatosis 1 / Predisposición Genética a la Enfermedad Tipo de estudio: Diagnostic_studies / Guideline / Prognostic_studies Límite: Adult / Humans Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos