Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders

Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders Publisher Pubmed

Cali E¹ ; Quirin T² ; Rocca C¹ ; Efthymiou S¹ ; Riva A³ ; Marafi D^{4, 5} ; Zaki MS⁶ ; Suri M^{7, 8} ; Dominguez R⁹ ; Elbendary HM⁶ ; Alavi S^{1, 10} ; Abdelhamid MS¹¹ ; Morsy H^{1, 12} ; Mauthem FT^{13, 14} Show All Authors

Cali E¹
Quirin T²
Rocca C¹
Efthymiou S¹
Riva A³
Marafi D^{4, 5}
Zaki MS⁶
Suri M^{7, 8}
Dominguez R⁹
Elbendary HM⁶
Alavi S^{1, 10}
Abdelhamid MS¹¹
Morsy H^{1, 12}
Mauthem FT^{13, 14}
Nizon M^{15, 16}
Tesner P¹⁷
Ryba L¹⁷
Zafar F¹⁸
Rana N¹⁸
Saadi NW¹⁹
Firoozfar Z¹⁰
Gencpinar P²⁰
Unay B²¹
Ustun C²¹
Bruel AL^{22, 23}
Coubes C²⁴
Stefanich J²⁵
Sezer O²⁶
Agolini E²⁷
Novelli A²⁷
Vasco G²⁸
Lettori D²⁸
Milh M²⁹
Villard L³⁰
Zeidler S³¹
Opperman H³²
Strehlow V³²
Issa MY⁶
El Khassab H³³
Chand P³⁴
Ibrahim S³⁴
Rashidinezhad A^{35, 36}
Miryounesi M³⁷
Larki P³⁷
Morrison J³⁸
Cristian I³⁸
Thiffault I^{39, 40, 41}
Bertsch NL⁴²
Noh GJ⁴³
Pappas J^{44, 45}
Moran E⁴⁶
Marinakis NM⁴⁷
Traegersynodinos J⁴⁷
Hosseini S⁴⁸
Abbaszadegan MR⁴⁹
Caumes R⁵⁰
Vissers LELM^{51, 52}
Neshatdoust M⁵³
Montazer Zohour M⁵⁴
El Fahime E⁵⁵
Canavati C⁵⁶
Kamal L⁵⁶
Kanaan M⁵⁶
Askander O⁵⁷
Voinova V^{58, 59}
Levchenko O⁶⁰
Haider S⁶¹
Halbach SS⁶²
Elias Maia R⁶³
Mansoor S^{64, 65}
Jain V⁶⁶
Tawde S⁶⁷
Challa VSR⁶⁸
Gowda VK⁶⁸
Srinivasan VM⁶⁸
Victor LA⁶⁹
Pinerobanos B⁷⁰
Hague J⁷¹
Elawady HA⁷²
Maria De Miranda Henriquessouza A⁷³
Cheema HA⁷⁴
Anjum MN⁷⁴
Idkaidak S⁷⁵
Alqarajeh F⁷⁶
Atawneh O⁷⁶
Morshaked H⁷⁷
Harel T⁷⁷
Zifarelli G⁷⁸
Bauer P⁷⁸
Kok F⁷⁹
Kitajima JP⁷⁹
Monteiro F⁷⁹
Josahkian J⁷⁹
Lesca G^{80, 81}
Chatron N^{80, 81}
Ville D⁸²
Murphy D⁸³
Neul JL⁸⁴
Mullegama SV⁸⁵
Begtrup A⁸⁵
Herman I⁸⁶
Mitani T⁴
Posey JE⁴
Tay CG⁸⁷
Javed I⁸⁸
Carr L⁸⁹
Kanani F⁹⁰
Beecroft F⁹⁰
Hane L⁹¹
Abdelkreem E⁹²
Macek M¹⁷
Bispo L⁹³
Elmaksoud MA⁹⁴
Hashemigorji F⁹⁵
Pehlivan D^{4, 86}
Amor DJ⁹⁶
Jamra RA³²
Chung WK⁹⁷
Ghayoor Karimiani E^{98, 99, 100}
Campeau PM^{101, 102}
Alkuraya FS¹⁰³
Pagnamenta AT¹⁰⁴
Gleeson JG^{105, 106}
Lupski JR^{4, 107, 108}
Striano P^{3, 109}
Morenodeluca A¹¹⁰
Lafontaine DLJ²
Houlden H¹
Maroofian R¹

Source: Genetics in Medicine Published:2025

Abstract

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.” © 2024 The Authors

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Style	Citing Format
MLA	Cali E, et al.. "Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders." Genetics in Medicine, vol. , no. , 2025, pp. -.
APA	Cali E, Quirin T, Rocca C, Efthymiou S, Riva A, Marafi D, Zaki MS, Suri M, Dominguez R, Elbendary HM, Alavi S, Abdelhamid MS, Morsy H, Mauthem FT, Nizon M, Tesner P, Ryba L, Zafar F, Rana N, ... Maroofian R (2025). Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders. Genetics in Medicine, (), -.
Chicago	Cali E, Quirin T, Rocca C, Efthymiou S, Riva A, Marafi D, Zaki MS, et al.. "Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders." Genetics in Medicine , no. (2025): -.
Harvard	Cali E et al. (2025) 'Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders', Genetics in Medicine, (), pp. -.
Vancouver	Cali E, Quirin T, Rocca C, Efthymiou S, Riva A, Marafi D, et al.. Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders. Genetics in Medicine. 2025;():-.
BibTex	@article{ author = {Cali E and Quirin T and Rocca C and Efthymiou S and Riva A and Marafi D and Zaki MS and Suri M and Dominguez R and Elbendary HM and Alavi S and Abdelhamid MS and Morsy H and Mauthem FT and Nizon M and Tesner P and Ryba L and Zafar F and Rana N and Saadi NW and Firoozfar Z and Gencpinar P and Unay B and Ustun C and Bruel AL and Coubes C and Stefanich J and Sezer O and Agolini E and Novelli A and Vasco G and Lettori D and Milh M and Villard L and Zeidler S and Opperman H and Strehlow V and Issa MY and El Khassab H and Chand P and Ibrahim S and Rashidinezhad A and Miryounesi M and Larki P and Morrison J and Cristian I and Thiffault I and Bertsch NL and Noh GJ and Pappas J and Moran E and Marinakis NM and Traegersynodinos J and Hosseini S and Abbaszadegan MR and Caumes R and Vissers LELM and Neshatdoust M and Montazer Zohour M and El Fahime E and Canavati C and Kamal L and Kanaan M and Askander O and Voinova V and Levchenko O and Haider S and Halbach SS and Elias Maia R and Mansoor S and Jain V and Tawde S and Challa VSR and Gowda VK and Srinivasan VM and Victor LA and Pinerobanos B and Hague J and Elawady HA and Maria De Miranda Henriquessouza A and Cheema HA and Anjum MN and Idkaidak S and Alqarajeh F and Atawneh O and Morshaked H and Harel T and Zifarelli G and Bauer P and Kok F and Kitajima JP and Monteiro F and Josahkian J and Lesca G and Chatron N and Ville D and Murphy D and Neul JL and Mullegama SV and Begtrup A and Herman I and Mitani T and Posey JE and Tay CG and Javed I and Carr L and Kanani F and Beecroft F and Hane L and Abdelkreem E and Macek M and Bispo L and Elmaksoud MA and Hashemigorji F and Pehlivan D and Amor DJ and Jamra RA and Chung WK and Ghayoor Karimiani E and Campeau PM and Alkuraya FS and Pagnamenta AT and Gleeson JG and Lupski JR and Striano P and Morenodeluca A and Lafontaine DLJ and Houlden H and Maroofian R}, title = {Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders}, journal = {Genetics in Medicine}, volume = {}, number = {}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Cali E AU - Quirin T AU - Rocca C AU - Efthymiou S AU - Riva A AU - Marafi D AU - Zaki MS AU - Suri M AU - Dominguez R AU - Elbendary HM AU - Alavi S AU - Abdelhamid MS AU - Morsy H AU - Mauthem FT AU - Nizon M AU - Tesner P AU - Ryba L AU - Zafar F AU - Rana N AU - Saadi NW AU - Firoozfar Z AU - Gencpinar P AU - Unay B AU - Ustun C AU - Bruel AL AU - Coubes C AU - Stefanich J AU - Sezer O AU - Agolini E AU - Novelli A AU - Vasco G AU - Lettori D AU - Milh M AU - Villard L AU - Zeidler S AU - Opperman H AU - Strehlow V AU - Issa MY AU - El Khassab H AU - Chand P AU - Ibrahim S AU - Rashidinezhad A AU - Miryounesi M AU - Larki P AU - Morrison J AU - Cristian I AU - Thiffault I AU - Bertsch NL AU - Noh GJ AU - Pappas J AU - Moran E AU - Marinakis NM AU - Traegersynodinos J AU - Hosseini S AU - Abbaszadegan MR AU - Caumes R AU - Vissers LELM AU - Neshatdoust M AU - Montazer Zohour M AU - El Fahime E AU - Canavati C AU - Kamal L AU - Kanaan M AU - Askander O AU - Voinova V AU - Levchenko O AU - Haider S AU - Halbach SS AU - Elias Maia R AU - Mansoor S AU - Jain V AU - Tawde S AU - Challa VSR AU - Gowda VK AU - Srinivasan VM AU - Victor LA AU - Pinerobanos B AU - Hague J AU - Elawady HA AU - Maria De Miranda Henriquessouza A AU - Cheema HA AU - Anjum MN AU - Idkaidak S AU - Alqarajeh F AU - Atawneh O AU - Morshaked H AU - Harel T AU - Zifarelli G AU - Bauer P AU - Kok F AU - Kitajima JP AU - Monteiro F AU - Josahkian J AU - Lesca G AU - Chatron N AU - Ville D AU - Murphy D AU - Neul JL AU - Mullegama SV AU - Begtrup A AU - Herman I AU - Mitani T AU - Posey JE AU - Tay CG AU - Javed I AU - Carr L AU - Kanani F AU - Beecroft F AU - Hane L AU - Abdelkreem E AU - Macek M AU - Bispo L AU - Elmaksoud MA AU - Hashemigorji F AU - Pehlivan D AU - Amor DJ AU - Jamra RA AU - Chung WK AU - Ghayoor Karimiani E AU - Campeau PM AU - Alkuraya FS AU - Pagnamenta AT AU - Gleeson JG AU - Lupski JR AU - Striano P AU - Morenodeluca A AU - Lafontaine DLJ AU - Houlden H AU - Maroofian R TI - Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders JO - Genetics in Medicine VL - IS - SP - EP - PY - 2025 ER -

Style

Citing Format

MLA

Cali E, et al.. "Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders." Genetics in Medicine, vol. , no. , 2025, pp. -.

APA

Cali E, Quirin T, Rocca C, Efthymiou S, Riva A, Marafi D, Zaki MS, Suri M, Dominguez R, Elbendary HM, Alavi S, Abdelhamid MS, Morsy H, Mauthem FT, Nizon M, Tesner P, Ryba L, Zafar F, Rana N, ... Maroofian R (2025). Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders. Genetics in Medicine, (), -.

Chicago

Cali E, Quirin T, Rocca C, Efthymiou S, Riva A, Marafi D, Zaki MS, et al.. "Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders." Genetics in Medicine , no. (2025): -.

Harvard

Cali E et al. (2025) 'Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders', Genetics in Medicine, (), pp. -.

Vancouver

Cali E, Quirin T, Rocca C, Efthymiou S, Riva A, Marafi D, et al.. Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders. Genetics in Medicine. 2025;():-.

BibTex

@article{ author = {Cali E and Quirin T and Rocca C and Efthymiou S and Riva A and Marafi D and Zaki MS and Suri M and Dominguez R and Elbendary HM and Alavi S and Abdelhamid MS and Morsy H and Mauthem FT and Nizon M and Tesner P and Ryba L and Zafar F and Rana N and Saadi NW and Firoozfar Z and Gencpinar P and Unay B and Ustun C and Bruel AL and Coubes C and Stefanich J and Sezer O and Agolini E and Novelli A and Vasco G and Lettori D and Milh M and Villard L and Zeidler S and Opperman H and Strehlow V and Issa MY and El Khassab H and Chand P and Ibrahim S and Rashidinezhad A and Miryounesi M and Larki P and Morrison J and Cristian I and Thiffault I and Bertsch NL and Noh GJ and Pappas J and Moran E and Marinakis NM and Traegersynodinos J and Hosseini S and Abbaszadegan MR and Caumes R and Vissers LELM and Neshatdoust M and Montazer Zohour M and El Fahime E and Canavati C and Kamal L and Kanaan M and Askander O and Voinova V and Levchenko O and Haider S and Halbach SS and Elias Maia R and Mansoor S and Jain V and Tawde S and Challa VSR and Gowda VK and Srinivasan VM and Victor LA and Pinerobanos B and Hague J and Elawady HA and Maria De Miranda Henriquessouza A and Cheema HA and Anjum MN and Idkaidak S and Alqarajeh F and Atawneh O and Morshaked H and Harel T and Zifarelli G and Bauer P and Kok F and Kitajima JP and Monteiro F and Josahkian J and Lesca G and Chatron N and Ville D and Murphy D and Neul JL and Mullegama SV and Begtrup A and Herman I and Mitani T and Posey JE and Tay CG and Javed I and Carr L and Kanani F and Beecroft F and Hane L and Abdelkreem E and Macek M and Bispo L and Elmaksoud MA and Hashemigorji F and Pehlivan D and Amor DJ and Jamra RA and Chung WK and Ghayoor Karimiani E and Campeau PM and Alkuraya FS and Pagnamenta AT and Gleeson JG and Lupski JR and Striano P and Morenodeluca A and Lafontaine DLJ and Houlden H and Maroofian R}, title = {Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders}, journal = {Genetics in Medicine}, volume = {}, number = {}, pages = {-}, year = {2025} }

RIS

TY - JOUR
AU - Cali E
AU - Quirin T
AU - Rocca C
AU - Efthymiou S
AU - Riva A
AU - Marafi D
AU - Zaki MS
AU - Suri M
AU - Dominguez R
AU - Elbendary HM
AU - Alavi S
AU - Abdelhamid MS
AU - Morsy H
AU - Mauthem FT
AU - Nizon M
AU - Tesner P
AU - Ryba L
AU - Zafar F
AU - Rana N
AU - Saadi NW
AU - Firoozfar Z
AU - Gencpinar P
AU - Unay B
AU - Ustun C
AU - Bruel AL
AU - Coubes C
AU - Stefanich J
AU - Sezer O
AU - Agolini E
AU - Novelli A
AU - Vasco G
AU - Lettori D
AU - Milh M
AU - Villard L
AU - Zeidler S
AU - Opperman H
AU - Strehlow V
AU - Issa MY
AU - El Khassab H
AU - Chand P
AU - Ibrahim S
AU - Rashidinezhad A
AU - Miryounesi M
AU - Larki P
AU - Morrison J
AU - Cristian I
AU - Thiffault I
AU - Bertsch NL
AU - Noh GJ
AU - Pappas J
AU - Moran E
AU - Marinakis NM
AU - Traegersynodinos J
AU - Hosseini S
AU - Abbaszadegan MR
AU - Caumes R
AU - Vissers LELM
AU - Neshatdoust M
AU - Montazer Zohour M
AU - El Fahime E
AU - Canavati C
AU - Kamal L
AU - Kanaan M
AU - Askander O
AU - Voinova V
AU - Levchenko O
AU - Haider S
AU - Halbach SS
AU - Elias Maia R
AU - Mansoor S
AU - Jain V
AU - Tawde S
AU - Challa VSR
AU - Gowda VK
AU - Srinivasan VM
AU - Victor LA
AU - Pinerobanos B
AU - Hague J
AU - Elawady HA
AU - Maria De Miranda Henriquessouza A
AU - Cheema HA
AU - Anjum MN
AU - Idkaidak S
AU - Alqarajeh F
AU - Atawneh O
AU - Morshaked H
AU - Harel T
AU - Zifarelli G
AU - Bauer P
AU - Kok F
AU - Kitajima JP
AU - Monteiro F
AU - Josahkian J
AU - Lesca G
AU - Chatron N
AU - Ville D
AU - Murphy D
AU - Neul JL
AU - Mullegama SV
AU - Begtrup A
AU - Herman I
AU - Mitani T
AU - Posey JE
AU - Tay CG
AU - Javed I
AU - Carr L
AU - Kanani F
AU - Beecroft F
AU - Hane L
AU - Abdelkreem E
AU - Macek M
AU - Bispo L
AU - Elmaksoud MA
AU - Hashemigorji F
AU - Pehlivan D
AU - Amor DJ
AU - Jamra RA
AU - Chung WK
AU - Ghayoor Karimiani E
AU - Campeau PM
AU - Alkuraya FS
AU - Pagnamenta AT
AU - Gleeson JG
AU - Lupski JR
AU - Striano P
AU - Morenodeluca A
AU - Lafontaine DLJ
AU - Houlden H
AU - Maroofian R
TI - Clinical and Genetic Delineation of Autosomal Recessive and Dominant Actl6b-Related Developmental Brain Disorders
JO - Genetics in Medicine
VL -
IS -
SP -
EP -
PY - 2025
ER -

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Abstract