Journal article
The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder
Human mutation, Vol.43(2), pp.266-282
02/2022
DOI: 10.1002/humu.24308
PMID: 34859529
Abstract
De novo variants in QRICH1 (Glutamine-rich protein 1) has recently been reported in 11 individuals with intellectual disability (ID). The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum stress through transcriptional control of proteostasis. In this study, we present 27 additional individuals and delineate the clinical and molecular spectrum of the individuals (n = 38) with QRICH1 variants. The main clinical features were mild to moderate developmental delay/ID (71%), nonspecific facial dysmorphism (92%) and hypotonia (39%). Additional findings included poor weight gain (29%), short stature (29%), autism spectrum disorder (29%), seizures (24%) and scoliosis (18%). Minor structural brain abnormalities were reported in 52% of the individuals with brain imaging. Truncating or splice variants were found in 28 individuals and 10 had missense variants. Four variants were inherited from mildly affected parents. This study confirms that heterozygous QRICH1 variants cause a neurodevelopmental disorder including short stature and expands the phenotypic spectrum to include poor weight gain, scoliosis, hypotonia, minor structural brain anomalies, and seizures. Inherited variants from mildly affected parents are reported for the first time, suggesting variable expressivity.
Details
- Title: Subtitle
- The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder
- Creators
- Smitha Kumble - Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, AustraliaAmanda M Levy - Copenhagen University HospitalJaya Punetha - Baylor College of MedicineHua Gao - GeneDxNicholas Ah Mew - Rare Disease Institute, Children's National Hospital, Washington, District of Columbia, USAKwame Anyane-Yeboa - Columbia UniversityPaul J Benke - Boston Children's HospitalSara M Berger - Columbia UniversityLise Bjerglund - Department of Pediatrics, University Hospital Hvidovre, Hvidovre, DenmarkBelinda Campos-Xavier - Division of Genetic Medicine, Lausanne University Hospital and University of Lausanne (CHUV), Lausanne, SwitzerlandMichael Ciliberto - University of IowaJulie S Cohen - Kennedy Krieger InstituteAnne M Comi - Kennedy Krieger InstituteCynthia Curry - University of California, San FranciscoLena Damaj - Service de pédiatrie et de génétique clinique, CHU Rennes, Rennes, FranceAnne-Sophie Denommé-Pichon - University of BurgundyLisa Emrick - Baylor College of MedicineLaurence Faivre - Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Université de Bourgogne, Dijon, FranceMary Beth Fasano - University of IowaAlice Fiévet - Service Génétique des Tumeurs, Gustave Roussy, Villejuif, FranceRichard S Finkel - Nemours FoundationSixto García-Miñaúr - Hospital Universitario La PazAmanda Gerard - Baylor College of MedicinePaulino Gomez-Puertas - Spanish National Research CouncilMaria J Guillen Sacoto - Clinical Genomics Program, GeneDx, Maryland, USATrevor L Hoffman - Kaiser PermanenteLillian Howard - University of IowaAlejandro D Iglesias - Columbia UniversityKosuke Izumi - Children's Hospital of PhiladelphiaAustin Larson - University of Colorado DenverAnja Leiber - University of St. GallenReymundo Lozano - Icahn School of Medicine at Mount SinaiIñigo Marcos-Alcalde - Spanish National Research CouncilCassie S Mintz - Icahn School of Medicine at Mount SinaiSureni V Mullegama - GeneDxRikke S Møller - Department of Regional Health Research, University of Southern Denmark, Odense, DenmarkSylvie Odent - University of Rennes 1Henry Oppermann - Leipzig UniversityElsebet Ostergaard - Copenhagen University HospitalMarta Pacio-Míguez - Hospital Universitario La PazMaria Palomares-Bralo - Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, U753), Instituto Carlos III, Madrid, SpainSumit Parikh - Cleveland ClinicAnna M Paulson - University of IowaKonrad Platzer - Leipzig UniversityJennifer E Posey - Baylor College of MedicineLorraine Potocki - Baylor College of MedicineAnya Revah-Politi - Columbia University Medical CenterMarlene Rio - Hôpital Necker-Enfants MaladesAlyssa L Ritter - Children's Hospital of PhiladelphiaScott Robinson - Columbia UniversityJill A Rosenfeld - Baylor College of MedicineFernando Santos-Simarro - Hospital Universitario La PazSérgio B Sousa - University Clinic of Genetics, Faculty of Medicine, University of Coimbra, Coimbra, PortugalMathys Wéber - Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d'Enfants, CHU Dijon, Dijon, FranceYili Xie - GeneDxWendy K Chung - Columbia UniversityNatasha J Brown - The University of MelbourneZeynep Tümer - Copenhagen University HospitalUndiagnosed Diseases Network
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.43(2), pp.266-282
- DOI
- 10.1002/humu.24308
- PMID
- 34859529
- NLM abbreviation
- Hum Mutat
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Grant note
- UM1 HG006542 / NHGRI NIH HHS U01HG007709 / NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director UL1TR001873 / National Center for Advancing Translational Sciences, National Institutes of Health K08 HG008986 / NHGRI NIH HHS
- Language
- English
- Date published
- 02/2022
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology; Immunology; Neurology (Pediatrics); Internal Medicine
- Record Identifier
- 9984302205602771
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