Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/19603
Title: Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly identified patients and review of the literature.
Authors: Hemati, Parisa;Revah-Politi, Anya;Bassan, Haim;Petrovski, Slavé;Bilancia, Colleen G;Ramsey, Keri;Griffin, Nicole G;Bier, Louise;Cho, Megan T;Rosello, Monica;Lynch, Sally Ann;Colombo, Sophie;Weber, Astrid;Haug, Marte;Heinzen, Erin L;Sands, Tristan T;Narayanan, Vinodh;Primiano, Michelle;Aggarwal, Vimla S;Millan, Francisca;Sattler-Holtrop, Shannon G;Caro-Llopis, Alfonso;Pillar, Nir;Baker, Janice;Freedman, Rebecca;Kroes, Hester Y;Sacharow, Stephanie;Stong, Nick;Lapunzina, Pablo;Schneider, Michael C;Mendelsohn, Nancy J;Singleton, Amanda;Loik Ramey, Valerie;Wou, Karen;Kuzminsky, Alla;Monfort, Sandra;Weiss, Monica;Doyle, Samantha;Iglesias, Alejandro;Martinez, Francisco;Mckenzie, Fiona;Orellana, Carmen;van Gassen, Koen L I;Palomares, Maria;Bazak, Lily;Lee, Andy;Bircher, Ana;Basel-Vanagaite, Lina;Hafström, Maria;Houge, Gunnar;Goldstein, David B;Anyane-Yeboa, Kwame
Affiliation: DDD Study, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel
Department of Pediatrics, St Olav's Hospital, Trondheim, Norway
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
Institute for Genomic Medicine, Columbia University Medical Center, New York, New York
Pediatric Neurology & Development Center, Assaf Harofe Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York
Center for Rare Childhood Disorders, Translational Genomics Research Institute, Phoenix, Arizona
GeneDx, Gaithersburg, Maryland
Unidad de Genetica, Hospital Universitario y Politecnico La Fe, Valencia, Spain
Temple Street Children's University Hospital, Dublin, Ireland
Department of Clinical Genetics, Liverpool Women's Hospital, Liverpool, United Kingdom
Department of Medical Genetics, St. Olav's University Hospital, Trondheim, Norway
Department of Pediatrics, Children's Hospital of New York-Presbyterian, New York, New York
Carle Physician Group, Urbana, Illinois
Department of Genetics, Le Bonheur Children's Hospital, Memphis, Tennessee
Genomics Medicine Program, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota
Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, Western Australia, Australia
School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia
Department of Genetics, University Medical Center Utrecht, The Netherlands
Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts
INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, ISCIII, Madrid, Spain
Biochemical Genetics, Neurology Division, St Christopher's Hospital for Children, Philadelphia, Pennsylvania
Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center (CUMC), New York, New York
Child development Center, Clalit Health Service, Netanya, Israel
Brentwood Children's Clinic, Brentwood, Tennessee
Inner Vision Women's Ultrasound & Genetics, Nashville, Tennessee
Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 8-Sep-2018
EDate: 2018
Citation: American journal of medical genetics. Part A 2018; online first: 8 September
Abstract: De novo germline mutations in GNB1 have been associated with a neurodevelopmental phenotype. To date, 28 patients with variants classified as pathogenic have been reported. We add 18 patients with de novo mutations to this cohort, including a patient with mosaicism for a GNB1 mutation who presented with a milder phenotype. Consistent with previous reports, developmental delay in these patients was moderate to severe, and more than half of the patients were non-ambulatory and nonverbal. The most observed substitution affects the p.Ile80 residue encoded in exon 6, with 28% of patients carrying a variant at this residue. Dystonia and growth delay were observed more frequently in patients carrying variants in this residue, suggesting a potential genotype-phenotype correlation. In the new cohort of 18 patients, 50% of males had genitourinary anomalies and 61% of patients had gastrointestinal anomalies, suggesting a possible association of these findings with variants in GNB1. In addition, cutaneous mastocytosis, reported once before in a patient with a GNB1 variant, was observed in three additional patients, providing further evidence for an association to GNB1. We will review clinical and molecular data of these new cases and all previously reported cases to further define the phenotype and establish possible genotype-phenotype correlations.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19603
DOI: 10.1002/ajmg.a.40472
ORCID: 0000-0002-1527-961X
0000-0001-6347-552X
0000-0002-4977-9719
0000-0002-3328-4252
0000-0002-6102-1513
PubMed URL: 30194818
Type: Journal Article
Subjects: GNB1
developmental disabilities
hypotonia
mastocytosis
seizures
whole exome sequencing
Appears in Collections:Journal articles

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