Munuera-Cabeza, M.; Álvarez-Córdoba, M.; Suárez-Rivero, J.M.; Povea-Cabello, S.; Villalón-García, I.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Reche-López, D.; Cilleros-Holgado, P.; Piñero-Pérez, R.; Sánchez-Alcázar, J.A. Pantothenate and L-Carnitine Supplementation Improves Pathological Alterations in Cellular Models of KAT6A Syndrome. Genes2022, 13, 2300.
Munuera-Cabeza, M.; Álvarez-Córdoba, M.; Suárez-Rivero, J.M.; Povea-Cabello, S.; Villalón-García, I.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Reche-López, D.; Cilleros-Holgado, P.; Piñero-Pérez, R.; Sánchez-Alcázar, J.A. Pantothenate and L-Carnitine Supplementation Improves Pathological Alterations in Cellular Models of KAT6A Syndrome. Genes 2022, 13, 2300.
Munuera-Cabeza, M.; Álvarez-Córdoba, M.; Suárez-Rivero, J.M.; Povea-Cabello, S.; Villalón-García, I.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Reche-López, D.; Cilleros-Holgado, P.; Piñero-Pérez, R.; Sánchez-Alcázar, J.A. Pantothenate and L-Carnitine Supplementation Improves Pathological Alterations in Cellular Models of KAT6A Syndrome. Genes2022, 13, 2300.
Munuera-Cabeza, M.; Álvarez-Córdoba, M.; Suárez-Rivero, J.M.; Povea-Cabello, S.; Villalón-García, I.; Talaverón-Rey, M.; Suárez-Carrillo, A.; Reche-López, D.; Cilleros-Holgado, P.; Piñero-Pérez, R.; Sánchez-Alcázar, J.A. Pantothenate and L-Carnitine Supplementation Improves Pathological Alterations in Cellular Models of KAT6A Syndrome. Genes 2022, 13, 2300.
Abstract
Autism Spectrum disorder (ASD) and intellectual disability (ID) are the most frequent develop-mental disorders with a prevalence between 3% and 5% of the population. In addition, both ASD and ID can be found in the same patient. Mutations in several genes involved in the epigenetic regulation of gene expression have been linked to different ID associated with ASD features including alterations of the ly-sine-acetyltransferase 6A (KAT6A) gene in KAT6A syndrome. KAT6A enzyme participates in a wide range of critical cellular functions such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiolog-ical alterations in fibroblasts derived from three patients harboring KAT6A mutations. We ad-dressed survival in stress medium, histone acetylation, protein expression patterns and tran-scriptome analysis as well as cell bioenergetics. In addition, we evaluated the therapeutic effec-tiveness of epigenetic modulators and mitochondrial boosting agents such as pantothenate and L-carnitine in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly correct the mutant phe-notype in cellular models of KAT6A syndrome.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
3 December 2022
Commenter's Conflict of Interests:
I am a biochemical geneticist who first reported the value of carnitine and pantothenic acid in the treatment of KAT6A children and adults.
Comment:
This manuscript lacks citation of published KAT6A clinical research, including the use of carnitine and pantothenate (PMID 30724471, page 729, 2018), prescribed by KAT6A specialists since 2016, as described in the abstract. By citing this earlier publication and, thereby, linking new, supportive metabolic research to current clinical practice, physicians reluctant to offer this treatment to their KAT6A patients would be more willing to prescribe this simple and very effective treatment.
The commenter has declared there is no conflict of interests.
Comment:
We made reference to this Congress Abstract in the original paper. The reviewers recommended to us to delete it.
According to them: the reference was not a peer reviewed paper but an abstract from a meeting and therefore hard to validate.
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Commenter's Conflict of Interests: I am a biochemical geneticist who first reported the value of carnitine and pantothenic acid in the treatment of KAT6A children and adults.
Commenter:
The commenter has declared there is no conflict of interests.
According to them: the reference was not a peer reviewed paper but an abstract from a meeting and therefore hard to validate.