Dataset Information

Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants.

ABSTRACT:

Purpose

Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP.

Methods

Genetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the study. From these, detailed phenotypes for 52 previously unpublished individuals were collected and combined with 68 previously published individuals with comparable clinical information. The functional effects of selected CTNNB1 missense variants were assessed using TOPFlash assay.

Results

The phenotypes associated with pathogenic CTNNB1 variants were similar. A diagnosis of CP was not significantly associated with any set of traits that defined a specific phenotypic subgroup, indicating that CP is not additional to NEDSDV. Two CTNNB1 missense variants were dominant negative regulators of WNT signaling, highlighting the utility of the TOPFlash assay to functionally assess variants.

Conclusion

NEDSDV is a clinically homogeneous disorder irrespective of initial clinical diagnoses, including CP, or entry points for genetic testing.

SUBMITTER: Kayumi S

PROVIDER: S-EPMC9939054 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants.

Kayumi Sayaka S Pérez-Jurado Luis A LA Palomares María M Rangu Sneha S Sheppard Sarah E SE Chung Wendy K WK Kruer Michael C MC Kharbanda Mira M Amor David J DJ McGillivray George G Cohen Julie S JS García-Miñaúr Sixto S van Eyk Clare L CL Harper Kelly K Jolly Lachlan A LA Webber Dani L DL Barnett Christopher P CP Santos-Simarro Fernando F Pacio-Míguez Marta M Pozo Angela Del AD Bakhtiari Somayeh S Deardorff Matthew M Dubbs Holly A HA Izumi Kosuke K Grand Katheryn K Gray Christopher C Mark Paul R PR Bhoj Elizabeth J EJ Li Dong D Ortiz-Gonzalez Xilma R XR Keena Beth B Zackai Elaine H EH Goldberg Ethan M EM Perez de Nanclares Guiomar G Pereda Arrate A Llano-Rivas Isabel I Arroyo Ignacio I Fernández-Cuesta María Ángeles MÁ Thauvin-Robinet Christel C Faivre Laurence L Garde Aurore A Mazel Benoit B Bruel Ange-Line AL Tress Michael L ML Brilstra Eva E Fine Amena Smith AS Crompton Kylie E KE Stegmann Alexander P A APA Sinnema Margje M Stevens Servi C J SCJ Nicolai Joost J Lesca Gaetan G Lion-François Laurence L Haye Damien D Chatron Nicolas N Piton Amelie A Nizon Mathilde M Cogne Benjamin B Srivastava Siddharth S Bassetti Jennifer J Muss Candace C Gripp Karen W KW Procopio Rebecca A RA Millan Francisca F Morrow Michelle M MM Assaf Melissa M Moreno-De-Luca Andres A Joss Shelagh S Hamilton Mark J MJ Bertoli Marta M Foulds Nicola N McKee Shane S MacLennan Alastair H AH Gecz Jozef J Corbett Mark A MA

Genetics in medicine : official journal of the American College of Medical Genetics 20220909 11

<h4>Purpose</h4>Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP.<h4>Methods</h4>Genetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the stu ...[more]

PMID: 36083290

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Dataset Information

Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants.

Purpose

Methods

Results

Conclusion

Publications

Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants.

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