Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.

Autor:	Sarli C; Department of Translational Medicine, Federico II University of Naples, Naples, Italy., van der Laan L; Department of Human Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Reilly J; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada., Trajkova S; Department of Medical Sciences, University of Torino, Turin, Italy.; Molecular Biotechnology Center 'Guido Tarone', University of Turin, Turin, Italy., Carli D; Department of Medical Sciences, University of Torino, Turin, Italy., Brusco A; Department of Medical Sciences, University of Torino, Turin, Italy.; Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Turin, Italy.; Department of Neurosciences Rita Levi-Montalcini, University of Turin, Turin, Italy., Levy MA; Verspeeten Clinical Genome Centre, London Health Science Centre, London, Ontario, Canada., Relator R; Verspeeten Clinical Genome Centre, London Health Science Centre, London, Ontario, Canada., Kerkhof J; Verspeeten Clinical Genome Centre, London Health Science Centre, London, Ontario, Canada., McConkey H; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.; Verspeeten Clinical Genome Centre, London Health Science Centre, London, Ontario, Canada., Tedder ML; Greenwood Genetic Center, Greenwood, South Carolina, USA., Skinner C; Greenwood Genetic Center, Greenwood, South Carolina, USA., Alders M; Department of Human Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Henneman P; Department of Human Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Hennekam RCM; Department of Human Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Ciaccio C; Department of Pediatric Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., D'Arrigo S; Department of Pediatric Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Vitobello A; Department of Genetics, UNICAEN, Caen University Hospital, Normandy University, Caen, France., Faivre L; Université de Bourgogne, Inserm U1231, Equipe GAD, Dijon, France.; CHU Dijon Bourgogne, Centre de Génétique, Centre de Référence Maladies Rares 'Anomalies du Développement et Syndromes Malformatifs', FHU-TRANSLDAD, Dijon, France., Weber S; Service de Génétique, CHU de Caen-Normandie, Caen, France.; Service de Neurologie, CHU de Caen-Normandie, Caen, France., Vincent-Devulder A; Department of Genetics, UNICAEN, Caen University Hospital, Normandy University, Caen, France., Perrin L; Department of Genetics, UNICAEN, Caen University Hospital, Normandy University, Caen, France., Bourgois A; Department of Genetics, UNICAEN, Caen University Hospital, Normandy University, Caen, France., Yamamoto T; Division of Gene Medicine, Graduate School of Medical Science, Tokyo Women's Medical University, Tokyo, Japan., Metcalfe K; Manchester Centre for Genomic Medicine, St Mary's Hospital, Health Innovation Manchester, Manchester University Foundation NHS Trust, Manchester, UK.; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK., 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., Kini U; Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Oliveira D; Medical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal., Sousa SB; Medical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal., Williams D; Department of Clinical Genetics, Birmingham Women's & Children's NHS Foundation Trust, Birmingham, UK., Cappuccio G; Department of Translational Medicine, Federico II University of Naples, Naples, Italy., Sadikovic B; Department of Human Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.; Verspeeten Clinical Genome Centre, London Health Science Centre, London, Ontario, Canada., Brunetti-Pierri N; Department of Translational Medicine, Federico II University of Naples, Naples, Italy.; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.; Scuola Superiore Meridionale (SSM, School of Advanced Studies), Genomics and Experimental Medicine Program, University of Naples Federico II, Naples, Italy.
Jazyk:	angličtina
Zdroj:	American journal of medical genetics. Part C, Seminars in medical genetics [Am J Med Genet C Semin Med Genet] 2024 Dec; Vol. 196 (4), pp. e32089. Date of Electronic Publication: 2024 Jun 17.
DOI:	10.1002/ajmg.c.32089
Abstrakt:	Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures. (© 2024 The Author(s). American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)
Databáze:	MEDLINE
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