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Review
. 2025 Feb 18;52(1):242.
doi: 10.1007/s11033-025-10302-y.

Comprehensive review and outline of genotypes and phenotypes of Arboleda-Tham syndrome spectrum: insights from novel variants

Sahar Bayat  1 , Milad Gholami  2 , Hamidreza Khodadadi  3 , Mohammadreza Ghazavi  4 , Jafar Nasiri  4   5 , Majid Kheirollahi  6
Affiliations
Review

Comprehensive review and outline of genotypes and phenotypes of Arboleda-Tham syndrome spectrum: insights from novel variants

Sahar Bayat et al. Mol Biol Rep. .

Abstract

Background and objective: Mutations in the KAT6A gene, which encodes a histone acetyltransferase, have been linked to an autosomal dominant neurodevelopmental disorder known as the Arboleda-Tham syndrome. The clinical symptoms of this disorder are nonspecific and pose challenges to accurately characterizing the condition based solely on these symptoms. This study aimed to establish a definitive diagnosis in three patients with intellectual disability and multiple congenital anomalies, and to elucidate the genotype-phenotype correlation based on the existing literature.

Participants and methods: In this study, we investigated three probands with severe intellectual disability, global developmental delay, hypotonia, gait disturbance, microcephaly, scoliosis, abnormal heart morphology, strabismus, gastrointestinal dysmotility, and abnormal facial shape, using karyotype analysis, multiplex ligation-dependent probe amplification, and whole exome sequencing. We also conducted a comprehensive literature review of previously reported cases.

Results: The karyotype analysis and Multiplex ligation-dependent probe amplification results were normal. Whole exome sequencing revealed three novel de novo mutations, c.3712G > T (p.Glu1238*), c.3561 C > A (p.Cys1187*), and c.1069 C > T (p.Arg357*), in the KAT6A gene (NM_006766.5). The heterozygous variants were verified by Sanger sequencing and were not present in either parent.

Conclusions: In this study, we describe three cases of de novo KAT6A variants that were identified for the first time in Iran. Our results expand the understanding of the clinical features associated with Arboleda-Tham syndrome and validate the effectiveness of whole-exome sequencing to rapidly and accurately determine the etiology of such disorders. Furthermore, our literature review demonstrated close genotype-phenotype correlations associated with KAT6A and Arboleda-Tham syndrome.

Keywords: KAT6A; Arboleda-Tham syndrome; Intellectual disability; Multiple congenital anomalies; Whole exome sequencing.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures performed in the studies involving human participants were in accordance with the ethical standards of the local ethics committee of Isfahan University of Medical Science (IR.MUI.MED.REC.1402.398), as well as the 1964 Helsinki declaration. Written informed consent was obtained from the legal guardians of patients prior to sample collection. Consent for publication: was obtained from all the legal guardians of the individuals presented in this study. Competing interests: The authors declare no competing interests.

References

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