6533b858fe1ef96bd12b5aab
RESEARCH PRODUCT
The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder
Smitha KumbleAmanda LevyJaya PunethaHua GaoNicholas Ah MewKwame Anyane-yeboaPaul BenkeSara BergerLise BjerglundBelinda Campos-xavierMichael CilibertoJulie CohenAnne ComiCynthia CurryLena DamajAnne-sophie Denommé-pichonLisa EmrickLaurence FaivreMary Beth FasanoAlice FiévetRichard FinkelSixto García-miñaúrAmanda GerardPaulino Gomez-puertasMaria Guillen SacotoTrevor HoffmanLillian HowardAlejandro IglesiasKosuke IzumiAustin LarsonAnja LeiberReymundo LozanoIñigo Marcos-alcaldeCassie MintzSureni MullegamaRikke Rs MøllerSylvie OdentHenry OppermannElsebet OstergaardMarta Pacio-míguezMaria Palomares-braloSumit ParikhAnna PaulsonKonrad PlatzerJennifer PoseyLorraine PotockiAnya Revah-politiMarlene RioAlyssa RitterScott RobinsonJill RosenfeldFernando Santos-simarroKwame Anyane‐yeboaBelinda Campos‐xavierAnne‐sophie Denommé‐pichonSixto García‐miñaúrPaulino Gomez‐puertasIñigo Marcos‐alcaldeMarta Pacio‐míguezMaria Palomares‐braloAnya Revah‐politiFernando Santos‐simarroSérgio Sousa SombraMathys WéberYili XieWendy K. ChungNatasha BrownZeynep Tümersubject
Autism Spectrum Disorder[SDV]Life Sciences [q-bio]DwarfismBiologyBioinformaticsWeight GainShort stature03 medical and health sciences0302 clinical medicineNeurodevelopmental disorderNeuroimagingSeizuresvariable expressivityIntellectual disabilityGeneticsmedicineMissense mutationHumansQRICH1hypotoniaGenetics (clinical)030304 developmental biology0303 health sciencesmedicine.diseaseQRICH1Hypotoniashort statureScoliosisvariantAutism spectrum disorderNeurodevelopmental Disordersintellectual disabilityMuscle Hypotoniamedicine.symptom030217 neurology & neurosurgerydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-02-01 |