The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder

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The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder. / Kumble, Smitha; Undiagnosed Diseases Network.

In: Human Mutation, Vol. 43, No. 2, 2022, p. 266-282.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kumble, S & Undiagnosed Diseases Network 2022, 'The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder', Human Mutation, vol. 43, no. 2, pp. 266-282. https://doi.org/10.1002/humu.24308

APA

Kumble, S., & Undiagnosed Diseases Network (2022). The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder. Human Mutation, 43(2), 266-282. https://doi.org/10.1002/humu.24308

Vancouver

Kumble S, Undiagnosed Diseases Network. The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder. Human Mutation. 2022;43(2): 266-282. https://doi.org/10.1002/humu.24308

Author

Kumble, Smitha ; Undiagnosed Diseases Network. / The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder. In: Human Mutation. 2022 ; Vol. 43, No. 2. pp. 266-282.

Bibtex

@article{6884be2dcb264b10b3a9779a476c8cb5,
title = "The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder",
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 = "hypotonia, intellectual disability, QRICH1, short stature, variable expressivity, variant",
author = "Smitha Kumble and Levy, {Amanda M.} and Jaya Punetha and Hua Gao and {Ah Mew}, Nicholas and Kwame Anyane-Yeboa and Benke, {Paul J.} and Berger, {Sara M.} and Lise Bjerglund and Belinda Campos-Xavier and Michael Ciliberto and Cohen, {Julie S.} and Comi, {Anne M.} and Cynthia Curry and Lena Damaj and Denomm{\'e}-Pichon, {Anne Sophie} and Lisa Emrick and Laurence Faivre and Fasano, {Mary Beth} and Alice Fi{\'e}vet and Finkel, {Richard S.} and Sixto Garc{\'i}a-Mi{\~n}a{\'u}r and Amanda Gerard and Paulino Gomez-Puertas and {Guillen Sacoto}, {Maria J.} and Hoffman, {Trevor L.} and Lillian Howard and Iglesias, {Alejandro D.} and Kosuke Izumi and Austin Larson and Anja Leiber and Reymundo Lozano and I{\~n}igo Marcos-Alcalde and Mintz, {Cassie S.} and Mullegama, {Sureni V.} and M{\o}ller, {Rikke S.} and Sylvie Odent and Henry Oppermann and Elsebet Ostergaard and Marta Pacio-M{\'i}guez and Maria Palomares-Bralo and Sumit Parikh and Paulson, {Anna M.} and Konrad Platzer and Posey, {Jennifer E.} and Lorraine Potocki and Anya Revah-Politi and Marlene Rio and Ritter, {Alyssa L.} and Zeynep T{\"u}mer and {Undiagnosed Diseases Network}",
note = "Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC",
year = "2022",
doi = "10.1002/humu.24308",
language = "English",
volume = "43",
pages = " 266--282",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "JohnWiley & Sons, Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder

AU - Kumble, Smitha

AU - Levy, Amanda M.

AU - Punetha, Jaya

AU - Gao, Hua

AU - Ah Mew, Nicholas

AU - Anyane-Yeboa, Kwame

AU - Benke, Paul J.

AU - Berger, Sara M.

AU - Bjerglund, Lise

AU - Campos-Xavier, Belinda

AU - Ciliberto, Michael

AU - Cohen, Julie S.

AU - Comi, Anne M.

AU - Curry, Cynthia

AU - Damaj, Lena

AU - Denommé-Pichon, Anne Sophie

AU - Emrick, Lisa

AU - Faivre, Laurence

AU - Fasano, Mary Beth

AU - Fiévet, Alice

AU - Finkel, Richard S.

AU - García-Miñaúr, Sixto

AU - Gerard, Amanda

AU - Gomez-Puertas, Paulino

AU - Guillen Sacoto, Maria J.

AU - Hoffman, Trevor L.

AU - Howard, Lillian

AU - Iglesias, Alejandro D.

AU - Izumi, Kosuke

AU - Larson, Austin

AU - Leiber, Anja

AU - Lozano, Reymundo

AU - Marcos-Alcalde, Iñigo

AU - Mintz, Cassie S.

AU - Mullegama, Sureni V.

AU - Møller, Rikke S.

AU - Odent, Sylvie

AU - Oppermann, Henry

AU - Ostergaard, Elsebet

AU - Pacio-Míguez, Marta

AU - Palomares-Bralo, Maria

AU - Parikh, Sumit

AU - Paulson, Anna M.

AU - Platzer, Konrad

AU - Posey, Jennifer E.

AU - Potocki, Lorraine

AU - Revah-Politi, Anya

AU - Rio, Marlene

AU - Ritter, Alyssa L.

AU - Tümer, Zeynep

AU - Undiagnosed Diseases Network

N1 - Publisher Copyright: © 2021 Wiley Periodicals LLC

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - hypotonia

KW - intellectual disability

KW - QRICH1

KW - short stature

KW - variable expressivity

KW - variant

U2 - 10.1002/humu.24308

DO - 10.1002/humu.24308

M3 - Journal article

C2 - 34859529

AN - SCOPUS:85120961215

VL - 43

SP - 266

EP - 282

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 2

ER -

ID: 288197790