RESUMEN
Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.
Asunto(s)
Proteína de Unión a CREB , Proteína p300 Asociada a E1A , Síndrome de Rubinstein-Taybi , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/diagnóstico , Síndrome de Rubinstein-Taybi/terapia , Humanos , Proteína de Unión a CREB/genética , Proteína p300 Asociada a E1A/genética , Consenso , Manejo de la Enfermedad , MutaciónRESUMEN
PURPOSE: This study aims to assess the diagnostic utility and provide reporting recommendations for clinical DNA methylation episignature testing based on the cohort of patients tested through the EpiSign Clinical Testing Network. METHODS: The EpiSign assay utilized unsupervised clustering techniques and a support vector machine-based classification algorithm to compare each patient's genome-wide DNA methylation profile with the EpiSign Knowledge Database, yielding the result that was reported. An international working group, representing distinct EpiSign Clinical Testing Network health jurisdictions, collaborated to establish recommendations for interpretation and reporting of episignature testing. RESULTS: Among 2399 cases analyzed, 1667 cases underwent a comprehensive screen of validated episignatures, imprinting, and promoter regions, resulting in 18.7% (312/1667) positive reports. The remaining 732 referrals underwent targeted episignature analysis for assessment of sequence or copy-number variants (CNVs) of uncertain significance or for assessment of clinical diagnoses without confirmed molecular findings, and 32.4% (237/732) were positive. Cases with detailed clinical information were highlighted to describe various utility scenarios for episignature testing. CONCLUSION: Clinical DNA methylation testing including episignatures, imprinting, and promoter analysis provided by an integrated network of clinical laboratories enables test standardization and demonstrates significant diagnostic yield and clinical utility beyond DNA sequence analysis in rare diseases.
Asunto(s)
Metilación de ADN , Pruebas Genéticas , Enfermedades Raras , Humanos , Metilación de ADN/genética , Enfermedades Raras/genética , Enfermedades Raras/diagnóstico , Pruebas Genéticas/normas , Pruebas Genéticas/métodos , Femenino , Regiones Promotoras Genéticas/genética , Masculino , Variaciones en el Número de Copia de ADN/genética , Niño , Adulto , Preescolar , Impresión Genómica/genéticaRESUMEN
The European Society of Human Genetics (ESHG) was founded in 1967 as a professional organisation for members working in genetics in clinical practice, research and education. The Society seeks the integration of scientific research and its implementation into clinical practice and the education of specialists and the public in all areas of medical and human genetics. The Society works to do this through many approaches, including educational sessions at the annual conference; training courses in general and specialist areas of genetics; an online resource of educational materials (EuroGEMS); and a mentorship scheme. The ESHG Education Committee is implementing new approaches to expand the reach of its educational activities and portfolio. With changes in technology, appreciation of the utility of genomics in healthcare and the public's and patients' increased awareness of the role of genomics, this review will summarise how the ESHG is adapting to deliver innovative educational activity.
