Specifications and validation of the ACMG/AMP criteria for clinical interpretation of sequence variants in collagen genes associated with joint hypermobility.

Autor: Leone MP; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Morlino S; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Nardella G; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Pracella R; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Giachino D; Medical Genetics Unit, Department of Clinical and Biological Sciences, University of Turin, AOU 'S. Luigi Gonzaga', Orbassano, Turin, Italy., Celli L; Center for Rare Diseases, AOU Policlinico 'Umberto I', Rome, Italy., Baldo D; Medical Genetics Unit, AULSS2 Marca Trevigiana, Treviso, Italy., Turolla L; Medical Genetics Unit, AULSS2 Marca Trevigiana, Treviso, Italy., Piccione M; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.; Division of Medical Genetics, AOOR Villa Sofia-Cervello, Palermo, Italy., Salzano E; Division of Medical Genetics, AOOR Villa Sofia-Cervello, Palermo, Italy., Busè M; Division of Medical Genetics, AOOR Villa Sofia-Cervello, Palermo, Italy., Lastella P; Centro Sovraziendale Malattie Rare - UOC Medicina Interna Universitaria 'C. Frugoni' - AOU Policlinico Consorziale di Bari, Bari, Italy., Zollino M; Institute of Genomic Medicine, Department of Life Sciences and Public Health, 'Sacro Cuore' Catholic University of Rome, Rome, Italy.; Medical Genetics Unit, Foundation IRCCS AOU Policlinico 'A. Gemelli', Rome, Italy., Cantone R; Medical Genetics Unit, AOU 'Città della Salute e della Scienza' - 'Molinette' Hospital, Turin, Italy., Grosso E; Medical Genetics Unit, AOU 'Città della Salute e della Scienza' - 'Molinette' Hospital, Turin, Italy., Zonta A; Medical Genetics Unit, AOU 'Città della Salute e della Scienza' - 'Molinette' Hospital, Turin, Italy., Pasini B; Medical Genetics Unit, AOU 'Città della Salute e della Scienza' - 'Molinette' Hospital, Turin, Italy., Piscopo C; Medical and Laboratory Genetics Unit, AORN 'Antonio Cardarelli', Naples, Italy., De Maggio I; Medical and Laboratory Genetics Unit, AORN 'Antonio Cardarelli', Naples, Italy., Priolo M; Medical Genetics Unit, Grande Ospedale Metropolitano 'Bianchi Melacrino Morelli', Reggio Calabria, Italy., Mammi C; Medical Genetics Unit, Grande Ospedale Metropolitano 'Bianchi Melacrino Morelli', Reggio Calabria, Italy., Foiadelli T; Clinica Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Trabatti C; Division of Pediatrics, Azienda Socio Sanitaria Territoriale (ASST) Crema, Crema, Italy., Savasta S; Division of Pediatrics, Azienda Socio Sanitaria Territoriale (ASST) Crema, Crema, Italy., Iolascon A; Department of Molecular Medicine and Medical Biotechnologies, Federico II' University of Naples, Naples, Italy.; CEINGE Biotecnologie Avanzate, Naples, Italy., Ferraris A; Clinical Genetics Unit, UOC Laboratory of Medical Genetics, Department of Experimental Medicine at, Sapienza University, AO San Camillo-Forlanini, Rome, Italy., Lodato V; Clinical Genetics Unit, UOC Laboratory of Medical Genetics, Department of Experimental Medicine at, Sapienza University, AO San Camillo-Forlanini, Rome, Italy., Di Giosaffatte N; Clinical Genetics Unit, UOC Laboratory of Medical Genetics, Department of Experimental Medicine at, Sapienza University, AO San Camillo-Forlanini, Rome, Italy., Majore S; Clinical Genetics Unit, UOC Laboratory of Medical Genetics, Department of Experimental Medicine at, Sapienza University, AO San Camillo-Forlanini, Rome, Italy., Selicorni A; Department of Pediatrics, Center for Fragile Child, ASST Lariana Sant'Anna Hospital, Como, San Fermo della Battaglia, Italy., Petracca A; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Fusco C; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Celli M; Center for Rare Diseases, AOU Policlinico 'Umberto I', Rome, Italy., Guarnieri V; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Micale L; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy., Castori M; Division of Medical Genetics, Poliambulatorio 'Giovanni Paolo II', Fondazione IRCCS-Casa Sollievo della Sofferenza, Viale Padre Pio 7, 71013, San Giovanni Rotondo, Italy. m.castori@operapadrepio.it.
Jazyk: angličtina
Zdroj: Human genetics [Hum Genet] 2023 Jun; Vol. 142 (6), pp. 785-808. Date of Electronic Publication: 2023 Apr 20.
DOI: 10.1007/s00439-023-02547-z
Abstrakt: Deleterious variants in collagen genes are the most common cause of hereditary connective tissue disorders (HCTD). Adaptations of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria are still lacking. A multidisciplinary team was set up for developing specifications of the ACMG/AMP criteria for COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL11A1, COL11A2 and COL12A1, associated with various forms of HCTD featuring joint hypermobility, which is becoming one of the most common reasons of referral for molecular testing in this field. Such specifications were validated against 209 variants, and resulted effective for classifying as pathogenic and likely pathogenic null alleles without downgrading of the PVS1 level of strength and recurrent Glycine substitutions. Adaptations of selected criteria reduced uncertainties on private Glycine substitutions, intronic variants predicted to affect the splicing, and null alleles with a downgraded PVS1 level of strength. Segregation and multigene panel sequencing data mitigated uncertainties on non-Glycine substitutions by the attribution of one or more benignity criteria. These specifications may improve the clinical utility of molecular testing in HCTD by reducing the number of variants with neutral/conflicting interpretations. Close interactions between laboratory and clinicians are crucial to estimate the a priori utility of molecular test and to improve medical reports.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: