A case of KAT6A syndrome with a newly discovered mutation in the
            <i>KAT6A</i>
            gene, mainly manifested as bone marrow failure syndrome

Ai, Qi; Jiang, Lihua; Chen, Yun; Yao, Xiuyun; Yin, Jing; Chen, Sen

doi:10.1080/16078454.2023.2182159

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…Arboleda−Tham syndrome is caused by variants in KAT6A (lysine (K) acetyltransferase 6A;OMIM: 601408), which was first described by Arboleda et al ( 2015 ) and Tham et al ( 2015 ). Currently, KAT6A is the only gene associated with Arboleda‐Tham syndrome, and up to 100 pathogenic and likely pathogenic mutations have been identified (Ai et al, 2023 ; Kennedy et al, 2019 ), frequently with de‐novo occurrence (Kennedy et al, 2019 ; St John et al, 2022 ). Most patients of Arboleda−Tham syndrome are sporadic or autosomal dominant inheritance (Tham et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Simultaneously, they also had subtle facial manifestations including microretrognathia, thin upper lip, broad nasal tip, bi‐temporal narrowing, and low‐set/posteriorly rotated ears (St John et al, 2022 ; Tham et al, 2015 ). Additional clinical features of KAT6A syndrome also noted among the patient included sleep disturbances and behavioral abnormalities (Ai et al, 2023 ).…”

Section: Introductionmentioning

confidence: 90%

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Diagnosis of Arboleda‐Tham syndrome by whole‐exome sequencing in an Asian girl with severe developmental delay

Wang,

Zhang,

et al. 2024

Molec Gen & Gen Med

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ObjectiveThis study aims to report a severe phenotype of Arboleda‐Tham syndrome in a 20‐month‐old girl, characterized by global developmental delay, distinct facial features, intellectual disability. Arboleda‐Tham syndrome is known for its wide phenotypic spectrum and is associated with truncating variants in the KAT6A gene.MethodsTo diagnose this case, a combination of clinical phenotype assessment and whole‐exome sequencing technology was employed. The genetic analysis involved whole‐exome sequencing, followed by confirmation of the identified variant through Sanger sequencing.ResultsThe whole‐exome sequencing revealed a novel de novo frameshift mutation c.3048del (p.Leu1017Serfs*17) in the KAT6A gene, which is classified as likely pathogenic. This mutation was not found in the ClinVar and HGMD databases and was not present in her parents. The mutation leads to protein truncation or activation of nonsense‐mediated mRNA degradation. The mutation is located within exon 16, potentially leading to protein truncation or activation of nonsense‐mediated mRNA degradation. Protein modeling suggested that the de novo KAT6A mutation might alter hydrogen bonding and reduce protein stability, potentially damaging the protein structure and function.ConclusionThis study expands the understanding of the genetic basis of Arboleda‐Tham syndrome, highlighting the importance of whole‐exome sequencing in diagnosing cases with varied clinical presentations. The discovery of the novel KAT6A mutation adds to the spectrum of known pathogenic variants and underscores the significance of this gene in the syndrome's pathology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Diagnosis of Arboleda‐Tham syndrome by whole‐exome sequencing in an Asian girl with severe developmental delay

Wang,

Zhang,

et al. 2024

Molec Gen & Gen Med

View full text Add to dashboard Cite

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KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement

Tan,

Wang,

et al. 2024

Prog Orthod.

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Background Orthodontic tooth movement (OTM) is a dynamic equilibrium of bone remodeling, involving the osteogenesis of new bone and the osteoclastogenesis of old bone, which is mediated by mechanical force. Periodontal ligament stem cells (PDLCSs) in the periodontal ligament (PDL) space can transmit mechanical signals and regulate osteoclastogenesis during OTM. KAT6A is a histone acetyltransferase that plays a part in the differentiation of stem cells. However, whether KAT6A is involved in the regulation of osteoclastogenesis by PDLSCs remains unclear. Results In this study, we used the force-induced OTM model and observed that KAT6A was increased on the compression side of PDL during OTM, and also increased in PDLSCs under compression force in vitro. Repression of KAT6A by WM1119, a KAT6A inhibitor, markedly decreased the distance of OTM. Knockdown of KAT6A in PDLSCs decreased the RANKL/OPG ratio and osteoclastogenesis of THP-1. Mechanistically, KAT6A promoted osteoclastogenesis by binding and acetylating YAP, simultaneously regulating the YAP/TEAD axis and increasing the RANKL/OPG ratio in PDLSCs. TED-347, a YAP-TEAD4 interaction inhibitor, partly attenuated the elevation of the RANKL/OPG ratio induced by mechanical force. Conclusion Our study showed that the PDLSCs modulated osteoclastogenesis and increased the RANKL/OPG ratio under mechanical force through the KAT6A/YAP/TEAD4 pathway. KAT6A might be a novel target to accelerate OTM.

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A case of KAT6A syndrome with a newly discovered mutation in the KAT6A gene, mainly manifested as bone marrow failure syndrome

Cited by 2 publications

References 14 publications

Diagnosis of Arboleda‐Tham syndrome by whole‐exome sequencing in an Asian girl with severe developmental delay

Diagnosis of Arboleda‐Tham syndrome by whole‐exome sequencing in an Asian girl with severe developmental delay

KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement

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