@article{795e740c76f34aacaab7bfe60f031af0,
title = "The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder",
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.",
author = "{Undiagnosed Diseases Network} and Smitha Kumble and Levy, {Amanda M.} and Jaya Punetha and Hua Gao and {Ah Mew}, Nicholas and Kwame Anyane-Yeboa and Benke, {Paul J.} and Berger, {Sara M.} and Lise Bjerglund and Belinda Campos-Xavier and Michael Ciliberto and Cohen, {Julie S.} and Comi, {Anne M.} and Cynthia Curry and Lena Damaj and Denomm{\'e}-Pichon, {Anne Sophie} and Lisa Emrick and Laurence Faivre and Fasano, {Mary Beth} and Alice Fi{\'e}vet and Finkel, {Richard S.} and Sixto Garc{\'i}a-Mi{\~n}a{\'u}r and Amanda Gerard and Paulino Gomez-Puertas and {Guillen Sacoto}, {Maria J.} and Hoffman, {Trevor L.} and Lillian Howard and Iglesias, {Alejandro D.} and Kosuke Izumi and Austin Larson and Anja Leiber and Reymundo Lozano and I{\~n}igo Marcos-Alcalde and Mintz, {Cassie S.} and Mullegama, {Sureni V.} and M{\o}ller, {Rikke S.} and Sylvie Odent and Henry Oppermann and Elsebet Ostergaard and Marta Pacio-M{\'i}guez and Maria Palomares-Bralo and Sumit Parikh and Paulson, {Anna M.} and Konrad Platzer and Posey, {Jennifer E.} and Lorraine Potocki and Anya Revah-Politi and Marlene Rio and Ritter, {Alyssa L.} and Scott Robinson and Rosenfeld, {Jill A.} and Fernando Santos-Simarro and Sousa, {S{\'e}rgio B.} and Mathys W{\'e}ber and Yili Xie and Chung, {Wendy K.} and Brown, {Natasha J.} and Zeynep T{\"u}mer and Acosta, {Maria T.} and Margaret Adam and Adams, {David R.} and Agrawal, {Pankaj B.} and Alejandro, {Mercedes E.} and Justin Alvey and Laura Amendola and Ashley Andrews and Ashley, {Euan A.} and Azamian, {Mahshid S.} and Bacino, {Carlos A.} and Guney Bademci and Eva Baker and Ashok Balasubramanyam and Dustin Baldridge and Jim Bale and Michael Bamshad and Deborah Barbouth and Pinar Bayrak-Toydemir and Anita Beck and Beggs, {Alan H.} and Edward Behrens and Gill Bejerano and Jimmy Bennet and Beverly Berg-Rood and Bernstein, {Jonathan A.} and Berry, {Gerard T.} and Anna Bican and Stephanie Bivona and Elizabeth Blue and John Bohnsack and Carsten Bonnenmann and Devon Bonner and Lorenzo Botto and Brenna Boyd and Briere, {Lauren C.} and Elly Brokamp and Gabrielle Brown and Burke, {Elizabeth A.} and Burrage, {Lindsay C.} and Butte, {Manish J.} and Peter Byers and Byrd, {William E.} and John Carey and Olveen Carrasquillo and Chang, {Ta Chen Peter} and Sirisak Chanprasert and Chao, {Hsiao Tuan} and Clark, {Gary D.} and Coakley, {Terra R.} and Cobban, {Laurel A.} and Cogan, {Joy D.} and Matthew Coggins and Cole, {F. Sessions} and Colley, {Heather A.} and Cooper, {Cynthia M.} and Heidi Cope and Craigen, {William J.} and Crouse, {Andrew B.} and Michael Cunningham and Precilla D'Souza and Hongzheng Dai and Surendra Dasari and Joie Davis and Dayal, {Jyoti G.} and Matthew Deardorff and Dell'Angelica, {Esteban C.} and Dhar, {Shweta U.} and Katrina Dipple and Daniel Doherty and Naghmeh Dorrani and Doss, {Argenia L.} and Douine, {Emilie D.} and Draper, {David D.} and Laura Duncan and Dawn Earl and Eckstein, {David J.} and Emrick, {Lisa T.} and Eng, {Christine M.} and Cecilia Esteves and Marni Falk and Liliana Fernandez and Carlos Ferreira and Fieg, {Elizabeth L.} and Findley, {Laurie C.} and Fisher, {Paul G.} and Fogel, {Brent L.} and Irman Forghani and Laure Fresard and Gahl, {William A.} and Ian Glass and Bernadette Gochuico and Godfrey, {Rena A.} and Katie Golden-Grant and Goldman, {Alica M.} and Goldrich, {Madison P.} and Goldstein, {David B.} and Alana Grajewski and Groden, {Catherine A.} and Irma Gutierrez and Sihoun Hahn and Rizwan Hamid and Hanchard, {Neil A.} and Kelly Hassey and Nichole Hayes and Frances High and Anne Hing and Hisama, {Fuki M.} and Holm, {Ingrid A.} and Jason Hom and Martha Horike-Pyne and Alden Huang and Yong Huang and Laryssa Huryn and Rosario Isasi and Fariha Jamal and Jarvik, {Gail P.} and Jeffrey Jarvik and Suman Jayadev and Lefkothea Karaviti and Jennifer Kennedy and Dana Kiley and Kobren, {Shilpa N.} and Kohane, {Isaac S.} and Kohler, {Jennefer N.} and Deborah Krakow and Krasnewich, {Donna M.} and Elijah Kravets and Susan Korrick and Mary Koziura and Krier, {Joel B.} and Lalani, {Seema R.} and Byron Lam and Christina Lam and LaMoure, {Grace L.} and Lanpher, {Brendan C.} and Lanza, {Ian R.} and Stephen Pak and Timothy Schedl and Jimann Shin and Lilianna Solnica-Krezel and Jennifer Wambach",
note = "Funding Information: We thank Frederic Tran‐Mau‐Them (Inserm UMR1231 GAD, G{\'e}n{\'e}tique des Anomalies du D{\'e}veloppement, Universit{\'e} de Bourgogne, Dijon, France) for the RNA splicing experiments performed for individual 5. Jette Bune Rasmussen (Department of Clinical Genetics, Copenhagen University Hospital—Rigshospitalet) is acknowledged for her graphical support. Kathleen Pope (MD, Division of Genetics, Nemours Children's Hospital, USA) is acknowledged for the clinical information of individual 6 and El{\'e}onore Viora‐Dupont (Medical student, Centre de G{\'e}n{\'e}tique Clinique, CHU de Dijon) for the further clinical information of individuals 5 and 11. Part of this work has been generated within the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERNITHACA) [EU Framework Partnership Agreement ID: 3HP‐HP‐FPA ERN‐01‐2016/739516]. This study was supported by the National Human Genome Research Institute (NHGRI) and National Heart, Lung, and Blood Institute (NHLBI)'s grant (UM1 HG006542), the Rashid Family Fund, the Centro Portugal Regional Operational Programme (CENTRO 2020) through the European Regional Development Fund (ERDF), the Spanish Ministry of Science/State Research Agency projects (RTC‐2017‐6494‐1, RTI2018‐094434‐B‐I00, and DTS20‐00024), the European Commission JPIAMR projects CONNECT and AEPIC, the Raregenomics network through the Consejer{\'i}a de Educaci{\'o}n de la C. de Madrid (S2017/BMD‐3721), the European Social Fund to Mar{\'i}a Palomares‐Bralo, ISCIII, Ministerio de Ciencia e Innovaci{\'o}n (PI19/01681), the National Human Genome Research Institute (NHGRI) (K08 HG008986), the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR001873), the Undiagnosed Diseases Network, the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director (U01HG007709), and the SFARI and JPB Foundation. Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC.",
year = "2022",
month = feb,
doi = "10.1002/humu.24308",
language = "English",
volume = "43",
pages = "266--282",
journal = "Human Mutation",
issn = "1059-7794",
number = "2",
}