The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder

Smitha Kumble, Amanda M Levy, Jaya Punetha, Hua Gao, Nicholas Ah Mew, Kwame Anyane-Yeboa, Paul J Benke, Sara M Berger, Lise Bjerglund, Belinda Campos-Xavier, Michael Ciliberto, Julie S Cohen, Anne M Comi, Cynthia Curry, Lena Damaj, Anne-Sophie Denommé-Pichon, Lisa Emrick, Laurence Faivre, Mary Beth Fasano, Alice FiévetRichard S Finkel, Sixto García-Miñaúr, Amanda Gerard, Paulino Gomez-Puertas, Maria J Guillen Sacoto, Trevor L Hoffman, Lillian Howard, Alejandro D Iglesias, Kosuke Izumi, Austin Larson, Anja Leiber, Reymundo Lozano, Iñigo Marcos-Alcalde, Cassie S Mintz, Sureni V Mullegama, Rikke S Møller, Sylvie Odent, Henry Oppermann, Elsebet Ostergaard, Marta Pacio-Míguez, Maria Palomares-Bralo, Sumit Parikh, Anna M Paulson, Konrad Platzer, Jennifer E Posey, Lorraine Potocki, Anya Revah-Politi, Marlene Rio, Alyssa L Ritter, Scott Robinson, Jill A Rosenfeld, Fernando Santos-Simarro, Sérgio B Sousa, Mathys Wéber, Yili Xie, Wendy K Chung, Natasha J Brown, Zeynep Tümer*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


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.

Sider (fra-til)266-282
Antal sider17
TidsskriftHuman mutation
Udgave nummer2
Tidlig onlinedato2 dec. 2021
StatusUdgivet - feb. 2022

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© 2021 Wiley Periodicals LLC.


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