Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome
Abstract Brain development requires the coordinated growth of structures and cues that are essential for forming neural circuits and cognitive functions. The corpus callosum, the largest interhemispheric connection, is formed by the axons of callosal projection neurons through a series of tightly re...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2024-11-01
|
| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s44321-024-00178-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594475223875584 |
|---|---|
| author | Efil Bayam Peggy Tilly Stephan C Collins José Rivera Alvarez Meghna Kannan Lucile Tonneau Elena Brivio Bruno Rinaldi Romain Lecat Noémie Schwaller Ludovica Cotellessa Sateesh Maddirevula Fabiola Monteiro Carlos M Guardia João Paulo Kitajima Fernando Kok Mitsuhiro Kato Ahlam A A Hamed Mustafa A Salih Saeed Al Tala Mais O Hashem Hiroko Tada Hirotomo Saitsu Mariano Stabile Paolo Giacobini Sylvie Friant Zafer Yüksel Mitsuko Nakashima Fowzan S Alkuraya Binnaz Yalcin Juliette D Godin |
| author_facet | Efil Bayam Peggy Tilly Stephan C Collins José Rivera Alvarez Meghna Kannan Lucile Tonneau Elena Brivio Bruno Rinaldi Romain Lecat Noémie Schwaller Ludovica Cotellessa Sateesh Maddirevula Fabiola Monteiro Carlos M Guardia João Paulo Kitajima Fernando Kok Mitsuhiro Kato Ahlam A A Hamed Mustafa A Salih Saeed Al Tala Mais O Hashem Hiroko Tada Hirotomo Saitsu Mariano Stabile Paolo Giacobini Sylvie Friant Zafer Yüksel Mitsuko Nakashima Fowzan S Alkuraya Binnaz Yalcin Juliette D Godin |
| author_sort | Efil Bayam |
| collection | DOAJ |
| description | Abstract Brain development requires the coordinated growth of structures and cues that are essential for forming neural circuits and cognitive functions. The corpus callosum, the largest interhemispheric connection, is formed by the axons of callosal projection neurons through a series of tightly regulated cellular events, including neuronal specification, migration, axon extension and branching. Defects in any of those steps can lead to a range of disorders known as syndromic corpus callosum dysgenesis (CCD). We report five unrelated families carrying bi-allelic variants in WDR47 presenting with CCD together with other neuroanatomical phenotypes such as microcephaly and enlarged ventricles. Using in vitro and in vivo mouse models and complementation assays, we show that WDR47 is required for survival of callosal neurons by contributing to the maintenance of mitochondrial and microtubule homeostasis. We further propose that severity of the CCD phenotype is determined by the degree of the loss of function caused by the human variants. Taken together, we identify WDR47 as a causative gene of a new neurodevelopmental syndrome characterized by corpus callosum abnormalities and other neuroanatomical malformations. |
| format | Article |
| id | doaj-art-4825b143d3974af5a2d0c60faa5be790 |
| institution | Kabale University |
| issn | 1757-4684 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-4825b143d3974af5a2d0c60faa5be7902025-01-19T12:34:35ZengSpringer NatureEMBO Molecular Medicine1757-46842024-11-0117112916810.1038/s44321-024-00178-zBi-allelic variants in WDR47 cause a complex neurodevelopmental syndromeEfil Bayam0Peggy Tilly1Stephan C Collins2José Rivera Alvarez3Meghna Kannan4Lucile Tonneau5Elena Brivio6Bruno Rinaldi7Romain Lecat8Noémie Schwaller9Ludovica Cotellessa10Sateesh Maddirevula11Fabiola Monteiro12Carlos M Guardia13João Paulo Kitajima14Fernando Kok15Mitsuhiro Kato16Ahlam A A Hamed17Mustafa A Salih18Saeed Al Tala19Mais O Hashem20Hiroko Tada21Hirotomo Saitsu22Mariano Stabile23Paolo Giacobini24Sylvie Friant25Zafer Yüksel26Mitsuko Nakashima27Fowzan S Alkuraya28Binnaz Yalcin29Juliette D Godin30Institut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCInstitut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCInstitut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCInstitut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCInstitut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCUniversité de Bourgogne, INSERM UMR1231Institut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCUniversité de Strasbourg, CNRS, GMGM UMR7156Institut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCInstitut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCUniversité de Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition UMR-S 1172Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research CenterMendelics Análise Genomica SA, CEP 02511-000Placental Cell Biology Group, National Institute of Environmental Health Sciences, National Institutes of HealthMendelics Análise Genomica SA, CEP 02511-000Mendelics Análise Genomica SA, CEP 02511-000Department of Pediatrics, Showa University School of MedicineDepartment of Pediatric and Child Health, Faculty of Medicine University of KhartoumHealth Sector, King Abdulaziz City for Science and TechnologyDepartment of Pediatrics, Genetic Unit, Armed Forces HospitalDepartment of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research CenterDepartment of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical ScienceDepartment of Biochemistry, Hamamatsu University School of MedicineCenter of Genetics and Prenatal Diagnosis “Zygote”Université de Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition UMR-S 1172Université de Strasbourg, CNRS, GMGM UMR7156Human Genetics, Bioscientia GmbHDepartment of Biochemistry, Hamamatsu University School of MedicineDepartment of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research CenterInstitut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCInstitut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMCAbstract Brain development requires the coordinated growth of structures and cues that are essential for forming neural circuits and cognitive functions. The corpus callosum, the largest interhemispheric connection, is formed by the axons of callosal projection neurons through a series of tightly regulated cellular events, including neuronal specification, migration, axon extension and branching. Defects in any of those steps can lead to a range of disorders known as syndromic corpus callosum dysgenesis (CCD). We report five unrelated families carrying bi-allelic variants in WDR47 presenting with CCD together with other neuroanatomical phenotypes such as microcephaly and enlarged ventricles. Using in vitro and in vivo mouse models and complementation assays, we show that WDR47 is required for survival of callosal neurons by contributing to the maintenance of mitochondrial and microtubule homeostasis. We further propose that severity of the CCD phenotype is determined by the degree of the loss of function caused by the human variants. Taken together, we identify WDR47 as a causative gene of a new neurodevelopmental syndrome characterized by corpus callosum abnormalities and other neuroanatomical malformations.https://doi.org/10.1038/s44321-024-00178-zWDR47Corpus Callosum DysgenesisNeurodevelopmental DisorderCallosal NeuronsMicrotubule and Mitochondrial Homeostasis |
| spellingShingle | Efil Bayam Peggy Tilly Stephan C Collins José Rivera Alvarez Meghna Kannan Lucile Tonneau Elena Brivio Bruno Rinaldi Romain Lecat Noémie Schwaller Ludovica Cotellessa Sateesh Maddirevula Fabiola Monteiro Carlos M Guardia João Paulo Kitajima Fernando Kok Mitsuhiro Kato Ahlam A A Hamed Mustafa A Salih Saeed Al Tala Mais O Hashem Hiroko Tada Hirotomo Saitsu Mariano Stabile Paolo Giacobini Sylvie Friant Zafer Yüksel Mitsuko Nakashima Fowzan S Alkuraya Binnaz Yalcin Juliette D Godin Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome EMBO Molecular Medicine WDR47 Corpus Callosum Dysgenesis Neurodevelopmental Disorder Callosal Neurons Microtubule and Mitochondrial Homeostasis |
| title | Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome |
| title_full | Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome |
| title_fullStr | Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome |
| title_full_unstemmed | Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome |
| title_short | Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome |
| title_sort | bi allelic variants in wdr47 cause a complex neurodevelopmental syndrome |
| topic | WDR47 Corpus Callosum Dysgenesis Neurodevelopmental Disorder Callosal Neurons Microtubule and Mitochondrial Homeostasis |
| url | https://doi.org/10.1038/s44321-024-00178-z |
| work_keys_str_mv | AT efilbayam biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT peggytilly biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT stephanccollins biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT joseriveraalvarez biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT meghnakannan biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT luciletonneau biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT elenabrivio biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT brunorinaldi biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT romainlecat biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT noemieschwaller biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT ludovicacotellessa biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT sateeshmaddirevula biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT fabiolamonteiro biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT carlosmguardia biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT joaopaulokitajima biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT fernandokok biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT mitsuhirokato biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT ahlamaahamed biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT mustafaasalih biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT saeedaltala biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT maisohashem biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT hirokotada biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT hirotomosaitsu biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT marianostabile biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT paologiacobini biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT sylviefriant biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT zaferyuksel biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT mitsukonakashima biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT fowzansalkuraya biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT binnazyalcin biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome AT juliettedgodin biallelicvariantsinwdr47causeacomplexneurodevelopmentalsyndrome |