The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder.

Details

Serval ID
serval:BIB_4A256FE26284
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder.
Journal
Human mutation
Author(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.
Working group(s)
Undiagnosed Diseases Network
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Publication state
Published
Issued date
02/2022
Peer-reviewed
Oui
Volume
43
Number
2
Pages
266-282
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
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
Yes
Create date
11/12/2021 13:45
Last modification date
14/11/2023 8:09
Usage data