Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.

Autor:	Kaur M; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Blair J; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Devkota B; Illumina Inc, San Diego, California, USA., Fortunato S; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Clark D; Natera, Inc., Austin, Texas, USA., Lawrence A; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Kim J; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Do W; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Semeo B; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Katz O; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Mehta D; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Yamamoto N; Division of Otolaryngology, National Center for Child Health and Development, Tokyo, Japan., Schindler E; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Al Rawi Z; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Wallace N; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Wilde JJ; Emugen Therapeutics, Woburn, Massachusetts, USA., McCallum J; Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Liu J; Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Xu D; Hematologics Inc, Seattle, Washington, USA., Jackson M; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Rentas S; Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA., Tayoun AA; Al Jalila Genomics Center, Al Jalila Children's Hospital, Dubai, United Arab Emirates.; Center for Genomic Discovery, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates., Zhe Z; Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Abdul-Rahman O; Department of Genetic Medicine, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA., Allen B; Fullerton Genetics Center, Mission Health, Asheville, North Carolina, USA., Angula MA; Department of Pediatrics, NYU Langone Hospital-Long Island, Mineola, New York, USA., Anyane-Yeboa K; Pediatrics, Columbia University Irving Medical Center, New York, New York, USA., Argente J; Hospital Infantil Universitario Niño Jesús & Universidad Autónoma de Madrid, Madrid, Spain.; CIBER Fisiopatología de la obesidad y nutrición (CIBEROBN) and IMDEA Food Institute, Madrid, Spain., Arn PH; Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, Florida, USA., Armstrong L; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Medical Genetics, BC Women's Hospital, Vancouver, British Columbia, Canada., Basel-Salmon L; Rabin Medical Center-Beilinson Hospital, Raphael Recanati Genetics Institute, Petach Tikva, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Felsenstein Medical Research Center, Petach Tikva, Israel., Baynam G; Western Australian Register of Developmental Anomalies and Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Western Australia, Australia.; Faculty of Health and Medical Sciences, Division of Pediatrics and Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.; Rare Care Centre, Perth Children's Hospital, Perth, Western Australia, Australia., Bird LM; Department of Pediatrics, University of California San Diego, San Diego, California, USA.; Division of Genetics & Dysmophology, Rady Children's Hospital San Diego, San Diego, California, USA., Bruegger D; Department of Otolaryngology-Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas, USA., Ch'ng GS; Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia., Chitayat D; The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for SickKids, University of Toronto, Toronto, Ontario, Canada., Clark R; Department of Pediatrics, Division of Medical Genetics, Loma Linda University School of Medicine, Loma Linda, California, USA., Cox GF; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Dave U; R & D MILS International India, Mumbai, India., DeBaere E; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium., Field M; Genetics of Learning Disability Service, Hunter Genetics, Waratah, New South Wales, Australia., Graham JM Jr; Division of Medical Genetics, Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA., Gripp KW; Nemours Children's Health, Wilmington, Delaware, USA., Greenstein R; University of Connecticut Health Center, Farmington, Connecticut, USA., Gupta N; Division of Genetics, Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India., Heidenreich R; Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA., Hoffman J; Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts, USA., Hopkin RJ; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Jones KL; Division of Dysmorphology & Teratology, Department of Pediatrics, University of California San Diego School of Medicine, San Diego, California, USA., Jones MC; Department of Pediatrics, University of California San Diego, San Diego, California, USA.; Division of Genetics & Dysmophology, Rady Children's Hospital San Diego, San Diego, California, USA., Kariminejad A; Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran., Kogan J; Division of Genetics, Advocate Children's Hospital, Park Ridge, Illinois, USA., Lace B; Children's Clinical University Hospital, Riga, Latvia., Leroy J; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium., Lynch SA; Department of Clinical Genetics, Children's Health Ireland, Dublin, Ireland., McDonald M; Duke University Medical Center, Durham, North Carolina, USA., Meagher K; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Mendelsohn N; Complex Health Solutions, United Healthcare, Minneapolis, Minnesota, USA., Micule I; Children's Clinical University Hospital, Riga, Latvia., Moeschler J; Department of Pediatrics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA., Nampoothiri S; Department of Pediatric Genetics, Amrita Institute of Medical Sciences & Research Centre, Cochin, India., Ohashi K; Department of Medical Genetics, BC Women's Hospital, Vancouver, British Columbia, Canada., Powell CM; Division of Genetics and Metabolism, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Ramanathan S; Department of Pediatrics, Division of Medical Genetics, Loma Linda University School of Medicine, Loma Linda, California, USA., Raskin S; Genetika-Centro de aconselhamento e laboratório de genética, Curitiba, Brazil., Roeder E; Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, San Antonio, Texas, USA., Rio M; Department of Genetics, Hôpital Necker-Enfants Malades, Paris, France., Rope AF; Genome Medical, South San Francisco, California, USA., Sangha K; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Scheuerle AE; Division of Genetics and Metabolism, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Schneider A; Department of Pediatrics and Oculogenetics, Wills Eye Hospital, Philadelphia, Pennsylvania, USA., Shalev S; Rappaport Faculty of Medicine, Technion, The Genetics Institute, Emek Medical Center, Afula, Haifa, Israel., Siu V; London Health Sciences Centre, London, Ontario, Canada.; Division of Medical Genetics, Department of Pediatrics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada., Smith R; Division of Genetics, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA., Stevens C; Department of Pediatrics, University of Tennessee College of Medicine, T.C. Thompson Children's Hospital, Chattanooga, Tennessee, USA., Tkemaladze T; Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia., Toimie J; Clinical Genetics Service, Laboratory Medicine Building, Southern General Hospital, Glasgow, UK., Toriello H; Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, USA., Turner A; Centre for Clinical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia.; Division of Genetics, Arnold Palmer Hospital, Orlando, Florida, USA., Wheeler PG; Division of Genetics, Arnold Palmer Hospital, Orlando, Florida, USA., White SM; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Australia.; Department of Paediatrics, University of Melbourne, Parkville, Australia., Young T; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Research to Prevent Blindness Inc, New York, New York, USA., Loomes KM; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Pipan M; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Behavioral Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Harrington AT; Center for Rehabilitation, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Zackai E; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Rajagopalan R; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Department of Pathology and Laboratory Medicine, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Conlin L; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Department of Pathology and Laboratory Medicine, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Deardorff MA; Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.; Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA., McEldrew D; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Pie J; Laboratorio de Genética Clínica y Genómica Funcional, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain., Ramos F; Unidad de Genética Clínica, Servicio de Pediatría, Hospital Clínico Universitario 'Lozano Blesa', Zaragoza, Spain.; Departamento de Pediatría, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain., Musio A; Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Pisa., Kline AD; Greater Baltimore Medical Centre, Harvey Institute of Human Genetics, Baltimore, Maryland, USA., Izumi K; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Raible SE; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Krantz ID; Division of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	American journal of medical genetics. Part A [Am J Med Genet A] 2023 Aug; Vol. 191 (8), pp. 2113-2131. Date of Electronic Publication: 2023 Jun 28.
DOI:	10.1002/ajmg.a.63247
Abstrakt:	Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (>60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or "DTRs"). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype-phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population. (© 2023 Wiley Periodicals LLC.)
Databáze:	MEDLINE
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