The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder.
Fiche publication
Date publication
décembre 2021
Journal
Human mutation
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence
Tous les auteurs :
Kumble S, Levy AM, Punetha J, Gao H, Mew NA, Anyane-Yeboa K, Benke PJ, Berger SM, Bjerglund L, Campos-Xavier B, Ciliberto M, Cohen JS, Comi AM, Curry C, Damaj L, Denommé-Pichon AS, Emrick L, Faivre L, Fasano MB, Fiévet A, Finkel RS, García-Miñaúr S, Gerard A, Gomez-Puertas P, Guillen Sacoto MJ, Hoffman TL, Howard L, Iglesias AD, Izumi K, Larson A, Leiber A, Lozano R, Marcos-Alcalde I, Mintz CS, Mullegama SV, Møller RS, Odent S, Oppermann H, Ostergaard E, Pacio-Míguez M, Palomares-Bralo M, Parikh S, Paulson AM, Platzer K, Posey JE, Potocki L, Revah-Politi A, Rio M, Ritter AL, Robinson S, Rosenfeld JA, Santos-Simarro F, Sousa SB, Network UD, Wéber M, Xie Y, Chung WK, Brown NJ, Tümer Z
Lien Pubmed
Résumé
De novo variants in QRICH1 (Glutamine-rich protein 1) has recently been reported in 11 individuals with intellectual disability. The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum (ER) 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/intellectual disability (71%), non-specific 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. This article is protected by copyright. All rights reserved.
Mots clés
QRICH1, hypotonia, intellectual disability, short stature, variable expressivity, variant
Référence
Hum Mutat. 2021 Dec 2;: