KAT7 variants cause deficient histone acetylation in a new neurodevelopmental disorder with cerebellar anomalies
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical Genetics
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Secondary Categories:
- Clinical Genetics
Introduction
Histone acetylation is a key aspect of epigenetic regulation. Genes of several lysine acetyltransferases, such as KAT5 (lysine acetyltransferase 5), KAT6A, and KAT6B, known for their roles in lysine acetylation of histones, are associated with neurodevelopmental disorders. KAT7 codes for a catalytic subunit of an important component of a tetrameric complex involved in the chromatin-modifying process.
Case Presentation
In this report, we describe 8 individuals with variants in KAT7 and neurodevelopmental disorders. Shared clinical features include developmental delays, and frequent dysarthria, ataxic gait, or cerebellar anomalies, underscoring a consistent phenotypic pattern.
Diagnostic Workup
The majority of individuals underwent exome sequencing. Among the individuals in our study, two have bi-allelic KAT7 variants, while six have de novo heterozygous variants.
Discussion
Structural analysis predicts deleterious impacts of these KAT7 variants, and in vitro biochemical studies has uncovered their negative functional effects on nucleosomal histone H3 acetylation at lysine 14. In parallel, it is worth noting that progressive cerebellar involvement has been observed in NEDFASB syndrome caused by monoallelic KAT5 mutations.
Conclusion
In conclusion, this case series establishes KAT7 as a causative gene for a neurodevelopmental disorder characterized by cerebellar involvement.
Histone acetylation is a key aspect of epigenetic regulation. Genes of several lysine acetyltransferases, such as KAT5 (lysine acetyltransferase 5), KAT6A, and KAT6B, known for their roles in lysine acetylation of histones, are associated with neurodevelopmental disorders. KAT7 codes for a catalytic subunit of an important component of a tetrameric complex involved in the chromatin-modifying process.
Case Presentation
In this report, we describe 8 individuals with variants in KAT7 and neurodevelopmental disorders. Shared clinical features include developmental delays, and frequent dysarthria, ataxic gait, or cerebellar anomalies, underscoring a consistent phenotypic pattern.
Diagnostic Workup
The majority of individuals underwent exome sequencing. Among the individuals in our study, two have bi-allelic KAT7 variants, while six have de novo heterozygous variants.
Discussion
Structural analysis predicts deleterious impacts of these KAT7 variants, and in vitro biochemical studies has uncovered their negative functional effects on nucleosomal histone H3 acetylation at lysine 14. In parallel, it is worth noting that progressive cerebellar involvement has been observed in NEDFASB syndrome caused by monoallelic KAT5 mutations.
Conclusion
In conclusion, this case series establishes KAT7 as a causative gene for a neurodevelopmental disorder characterized by cerebellar involvement.