The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder.

Détails

ID Serval
serval:BIB_4A256FE26284
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder.
Périodique
Human mutation
Auteur⸱e⸱s
Kumble S., Levy A.M., Punetha J., Gao H., Ah Mew N., Anyane-Yeboa K., Benke P.J., Berger S.M., Bjerglund L., Campos-Xavier B., Ciliberto M., Cohen J.S., Comi A.M., Curry C., Damaj L., Denommé-Pichon A.S., Emrick L., Faivre L., Fasano M.B., Fiévet A., Finkel R.S., García-Miñaúr S., Gerard A., Gomez-Puertas P., Guillen Sacoto M.J., Hoffman T.L., Howard L., Iglesias A.D., Izumi K., Larson A., Leiber A., Lozano R., Marcos-Alcalde I., Mintz C.S., Mullegama S.V., Møller R.S., Odent S., Oppermann H., Ostergaard E., Pacio-Míguez M., Palomares-Bralo M., Parikh S., Paulson A.M., Platzer K., Posey J.E., Potocki L., Revah-Politi A., Rio M., Ritter A.L., Robinson S., Rosenfeld J.A., Santos-Simarro F., Sousa S.B., Wéber M., Xie Y., Chung W.K., Brown N.J., Tümer Z.
Collaborateur⸱rice⸱s
Undiagnosed Diseases Network
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Statut éditorial
Publié
Date de publication
02/2022
Peer-reviewed
Oui
Volume
43
Numéro
2
Pages
266-282
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Autism Spectrum Disorder/genetics, Dwarfism, Humans, Intellectual Disability/genetics, Muscle Hypotonia, Neurodevelopmental Disorders/genetics, Scoliosis, Seizures, Weight Gain, QRICH1, hypotonia, intellectual disability, short stature, variable expressivity, variant
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/12/2021 13:45
Dernière modification de la notice
14/11/2023 8:09
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