The MAP3K7 gene: Further delineation of clinical characteristics and genotype/phenotype correlations.

Autor: van Woerden GM; Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.; Department of Clinical Genetics, The ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands., Senden R; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., de Konink C; Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Clinical Genetics, The ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands., Trezza RA; Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Clinical Genetics, The ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands., Baban A; Pediatric Cardiology and Cardiac Arrhythmias Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Bassetti JA; Division of Medical Genetics, Weill Cornell Medicine, New York City, New York, USA., van Bever Y; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.; Department of Clinical Genetics, The ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands., Bird LM; Department of Pediatrics, University of California San Diego, San Diego, California, USA.; Division of Genetics/Dysmorphology, Rady Children's Hospital San Diego, San Diego, California, USA., van Bon BW; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Brooks AS; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.; Department of Clinical Genetics, The ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands., Guan Q; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Klee EW; Division of Computational Biology, Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA., Marcelis C; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Rosado JM; Division of Computational Biology, Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA., Schimmenti LA; Department of Otorhinolaryngology Head and Neck Surgery, Ophthalmology, Clinical Genomics, and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA., Shikany AR; The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Terhal PA; Department of Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands., Nicole Weaver K; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Wessels MW; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., van Wieringen H; Department of Pediatrics, St. Antonius Hospital, Nieuwegein, The Netherlands., Hurst AC; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Gooch CF; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Steindl K; Institute of Medical Genetics, University of Zürich, Schlieren, Switzerland., Joset P; Department of Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland., Rauch A; Institute of Medical Genetics, University of Zürich, Schlieren, Switzerland., Tartaglia M; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy., Niceta M; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.; Department of Pediatrics, Sapienza University, Rome, Italy., Elgersma Y; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.; Department of Clinical Genetics, The ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, The Netherlands., Demirdas S; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2022 Oct; Vol. 43 (10), pp. 1377-1395. Date of Electronic Publication: 2022 Jul 29.
DOI: 10.1002/humu.24425
Abstrakt: Mitogen-activated protein 3 kinase 7 (MAP3K7) encodes the ubiquitously expressed transforming growth factor β-activated kinase 1, which plays a crucial role in many cellular processes. Mutationsin the MAP3K7 gene have been linked to two distinct disorders: frontometaphyseal dysplasia type 2 (FMD2) and cardiospondylocarpofacial syndrome (CSCF). The fact that different mutations can induce two distinct phenotypes suggests a phenotype/genotype correlation, but no side-by-side comparison has been done thus far to confirm this. Here, we significantly expand the cohort and the description of clinical phenotypes for patients with CSCF and FMD2 who carry mutations in MAP3K7. Our findings support that in contrast to FMD2-causing mutations, CSCF-causing mutations in MAP3K7 have a loss-of-function effect. Additionally, patients with pathogenic mutations in MAP3K7 are at risk for (severe) cardiac disease, have symptoms associated with connective tissue disease, and we show overlap in clinical phenotypes of CSCF with Noonan syndrome (NS). Together, we confirm a molecular fingerprint of FMD2- versus CSCF-causing MAP3K7 mutations and conclude that mutations in MAP3K7 should be considered in the differential diagnosis of patients with syndromic congenital cardiac defects and/or cardiomyopathy, syndromic connective tissue disorders, and in the differential diagnosis of NS.
(© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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