Медицинская библиотека · Genetics in medicine : official journal of the American College of Medical Genetics · 2024
Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.
Cali Elisa, Quirin Tania, Rocca Clarissa, Efthymiou Stephanie, Riva Antonella, Marafi Dana, Zaki Maha S, Suri Mohnish, Dominguez Roberto, Elbendary Hasnaa M, Alavi Shahryar, Abdel-Hamid Mohamed S, Morsy Heba, Mau-Them Frederic Tran, Nizon Mathilde, Tesner Pavel, Ryba Lukáš, Zafar Faisal, Rana Nuzhat, Saadi Nebal W, Firoozfar Zahra, Gencpinar Pinar, Unay Bulent, Ustun Canan, Bruel Ange-Line, Coubes Christine, Stefanich Jennifer, Sezer Ozlem, Agolini Emanuele, Novelli Antonio, Vasco Gessica, Lettori Donatella, Milh Mathieu, Villard Laurent, Zeidler Shimriet, Opperman Henry, Strehlow Vincent, Issa Mahmoud Y, El Khassab Hebatallah, Chand Prem, Ibrahim Shahnaz, Rashidi-Nezhad Ali, Miryounesi Mohammad, Larki Pegah, Morrison Jennifer, Cristian Ingrid, Thiffault Isabelle, Bertsch Nicole L, Noh Grace J, Pappas John, Moran Ellen, Marinakis Nikolaos M, Traeger-Synodinos Joanne, Hosseini Susan, Abbaszadegan Mohammad Reza, Caumes Roseline, Vissers Lisenka E L M, Neshatdoust Maedeh, Montazer Zohour Mostafa, El Fahime Elmostafa, Canavati Christina, Kamal Lara, Kanaan Moien, Askander Omar, Voinova Victoria, Levchenko Olga, Haider Shahzhad, Halbach Sara S, Elias Maia Rayana, Mansoor Salehi, Jain Vivek, Tawde Sanjukta, Challa Viveka Santhosh R, Gowda Vykuntaraju K, Srinivasan Varunvenkat M, Victor Lucas Alves, Pinero-Banos Benito, Hague Jennifer, ElAwady Heba Ahmed, Maria de Miranda Henriques-Souza Adelia, Cheema Huma Arshad, Anjum Muhammad Nadeem, Idkaidak Sara, Alqarajeh Firas, Atawneh Osama, Mor-Shaked Hagar, Harel Tamar, Zifarelli Giovanni, Bauer Peter, Kok Fernando, Kitajima Joao Paulo, Monteiro Fabiola, Josahkian Juliana, Lesca Gaetan, Chatron Nicolas, Ville Dorothe, Murphy David, Neul Jeffrey L, Mullegama Sureni V, Begtrup Amber, Herman Isabella, Mitani Tadahiro, Posey Jennifer E, Tay Chee Geap, Javed Iram, Carr Lucinda, Kanani Farah, Beecroft Fiona, Hane Lee, Abdelkreem Elsayed, Macek Milan, Bispo Luciana, Elmaksoud Marwa Abd, Hashemi-Gorji Farzad, Pehlivan Davut, Amor David J, Jamra Rami Abou, Chung Wendy K, Ghayoor Karimiani Eshan, Campeau Philippe M, Alkuraya Fowzan S, Pagnamenta Alistair T, Gleeson Joseph G, Lupski James R, Striano Pasquale, Moreno-De-Luca Andres, Lafontaine Denis L J, Houlden Henry, Maroofian Reza
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАМногоцентровое исследованиеПеревод в очереди
Аннотация
PURPOSE: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.
METHODS
We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.
RESULTS
Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe global developmental delay/intellectual disability, absent speech, and autistic features, whereas seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, and parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, particularly in pre-rRNA processing.
CONCLUSION
This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of "ribosomopathies."
Для цитирования: Cali Elisa, Quirin Tania, Rocca Clarissa, Efthymiou Stephanie, Riva Antonella, Marafi Dana, Zaki Maha S, Suri Mohnish, Dominguez Roberto, Elbendary Hasnaa M, Alavi Shahryar, Abdel-Hamid Mohamed S, Morsy Heba, Mau-Them Frederic Tran, Nizon Mathilde, Tesner Pavel, Ryba Lukáš, Zafar Faisal, Rana Nuzhat, Saadi Nebal W, Firoozfar Zahra, Gencpinar Pinar, Unay Bulent, Ustun Canan, Bruel Ange-Line, Coubes Christine, Stefanich Jennifer, Sezer Ozlem, Agolini Emanuele, Novelli Antonio, Vasco Gessica, Lettori Donatella, Milh Mathieu, Villard Laurent, Zeidler Shimriet, Opperman Henry, Strehlow Vincent, Issa Mahmoud Y, El Khassab Hebatallah, Chand Prem, Ibrahim Shahnaz, Rashidi-Nezhad Ali, Miryounesi Mohammad, Larki Pegah, Morrison Jennifer, Cristian Ingrid, Thiffault Isabelle, Bertsch Nicole L, Noh Grace J, Pappas John, Moran Ellen, Marinakis Nikolaos M, Traeger-Synodinos Joanne, Hosseini Susan, Abbaszadegan Mohammad Reza, Caumes Roseline, Vissers Lisenka E L M, Neshatdoust Maedeh, Montazer Zohour Mostafa, El Fahime Elmostafa, Canavati Christina, Kamal Lara, Kanaan Moien, Askander Omar, Voinova Victoria, Levchenko Olga, Haider Shahzhad, Halbach Sara S, Elias Maia Rayana, Mansoor Salehi, Jain Vivek, Tawde Sanjukta, Challa Viveka Santhosh R, Gowda Vykuntaraju K, Srinivasan Varunvenkat M, Victor Lucas Alves, Pinero-Banos Benito, Hague Jennifer, ElAwady Heba Ahmed, Maria de Miranda Henriques-Souza Adelia, Cheema Huma Arshad, Anjum Muhammad Nadeem, Idkaidak Sara, Alqarajeh Firas, Atawneh Osama, Mor-Shaked Hagar, Harel Tamar, Zifarelli Giovanni, Bauer Peter, Kok Fernando, Kitajima Joao Paulo, Monteiro Fabiola, Josahkian Juliana, Lesca Gaetan, Chatron Nicolas, Ville Dorothe, Murphy David, Neul Jeffrey L, Mullegama Sureni V, Begtrup Amber, Herman Isabella, Mitani Tadahiro, Posey Jennifer E, Tay Chee Geap, Javed Iram, Carr Lucinda, Kanani Farah, Beecroft Fiona, Hane Lee, Abdelkreem Elsayed, Macek Milan, Bispo Luciana, Elmaksoud Marwa Abd, Hashemi-Gorji Farzad, Pehlivan Davut, Amor David J, Jamra Rami Abou, Chung Wendy K, Ghayoor Karimiani Eshan, Campeau Philippe M, Alkuraya Fowzan S, Pagnamenta Alistair T, Gleeson Joseph G, Lupski James R, Striano Pasquale, Moreno-De-Luca Andres, Lafontaine Denis L J, Houlden Henry, Maroofian Reza. Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.. Genetics in medicine : official journal of the American College of Medical Genetics. 2024. DOI: 10.1016/j.gim.2024.101251.
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