Journal
HUMAN MUTATION
Volume 43, Issue 2, Pages 266-282Publisher
WILEY-HINDAWI
DOI: 10.1002/humu.24308
Keywords
hypotonia; intellectual disability; QRICH1; short stature; variable expressivity; variant
Categories
Funding
- Spanish Ministry of Science / State Research Agency projects [DTS20-00024, RTC-2017-6494-1, RTI2018-094434-B-I00]
- SFARI
- JPB Foundation
- Raregenomics network - Consejeria de Educacion de la C. de Madrid [S2017 / BMD-3721]
- European Comission JPIAMR project CONNECT
- European Comission JPIAMR project AEPIC
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR001873]
- National Human Genome Research Institute (NHGRI) [UM1 HG006542]
- National Heart, Lung, and Blood Institute (NHLBI) [UM1 HG006542]
- European Social Fund
- Rashid Family Fund
- NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director [U01HG007709]
- ISCIII, Ministerio de Ciencia e Innovacion [PI19/01681]
- Baylor Hopkins Center for Mendelian Genomics [NHGRI K08 HG008986, NHGRI/NLHBI UM1 HG006542]
- Centro Portugal Regional Operational Programme (CENTRO 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) [CENTRO-01-0247-FEDER-017800]
- Undiagnosed Diseases Network
Ask authors/readers for more resources
De novo variants in QRICH1 have been identified in individuals with intellectual disability, contributing to a neurodevelopmental disorder. The common clinical features include developmental delay, facial dysmorphism, and hypotonia, with additional findings of poor weight gain, short stature, autism spectrum disorder, seizures, and scoliosis. Some variants are inherited from mildly affected parents, suggesting variable expressivity.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available