The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder.
QRICH1
hypotonia
intellectual disability
short stature
variable expressivity
variant
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
09
11
2021
received:
03
06
2021
accepted:
28
11
2021
pubmed:
4
12
2021
medline:
30
4
2022
entrez:
3
12
2021
Statut:
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.
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
266-282Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG006542
Pays : United States
Organisme : NHGRI NIH HHS
ID : K08 HG008986
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007709
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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