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Journal Articles Human Mutation Year : 2022

The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder

Hua Gao
Nicholas Ah Mew
  • Function : Author
Kwame Anyane-Yeboa
  • Function : Author
Paul Benke
  • Function : Author
Sara Berger
  • Function : Author
Lise Bjerglund
  • Function : Author
Belinda Campos-Xavier
  • Function : Author
Michael Ciliberto
  • Function : Author
Julie Cohen
  • Function : Author
Anne Comi
  • Function : Author
Cynthia Curry
  • Function : Author
Mary Beth Fasano
  • Function : Author
Richard Finkel
  • Function : Author
Sixto García-Miñaúr
  • Function : Author
Amanda Gerard
  • Function : Author
Paulino Gomez-Puertas
  • Function : Author
Maria Guillen Sacoto
  • Function : Author
Trevor Hoffman
  • Function : Author
Lillian Howard
  • Function : Author
Alejandro Iglesias
  • Function : Author
Kosuke Izumi
Austin Larson
  • Function : Author
Anja Leiber
  • Function : Author
Reymundo Lozano
  • Function : Author
Iñigo Marcos-Alcalde
  • Function : Author
Cassie Mintz
  • Function : Author
Sureni Mullegama
  • Function : Author
Rikke Møller
Henry Oppermann
  • Function : Author
Elsebet Ostergaard
  • Function : Author
Marta Pacio-Míguez
  • Function : Author
Maria Palomares-Bralo
  • Function : Author
Sumit Parikh
  • Function : Author
Anna Paulson
  • Function : Author
Konrad Platzer
  • Function : Author
Jennifer Posey
Lorraine Potocki
  • Function : Author
Anya Revah-Politi
  • Function : Author
Marlene Rio
  • Function : Author
Alyssa Ritter
  • Function : Author
Scott Robinson
  • Function : Author
Jill Rosenfeld
Fernando Santos-Simarro
  • Function : Author
Kwame Anyane‐yeboa
  • Function : Author
Belinda Campos‐xavier
  • Function : Author
Anne‐sophie Denommé‐pichon
Sixto García‐miñaúr
  • Function : Author
Paulino Gomez‐puertas
  • Function : Author
Iñigo Marcos‐alcalde
  • Function : Author
Marta Pacio‐míguez
  • Function : Author
Maria Palomares‐bralo
  • Function : Author
Anya Revah‐politi
  • Function : Author
Sérgio Sousa Sombra
  • Function : Author
Wendy K. Chung
  • Function : Author
  • PersonId : 920701

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.
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Dates and versions

hal-03519376 , version 1 (26-01-2022)

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Attribution - NonCommercial

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Smitha Kumble, Amanda Levy, Jaya Punetha, Hua Gao, Nicholas Ah Mew, et al.. The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder. Human Mutation, 2022, 43 (2), pp.266-282. ⟨10.1002/humu.24308⟩. ⟨hal-03519376⟩
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