Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy

BACKGROUND: Lysine acetyltransferase 6B (KAT6B) encodes a highly conserved histone acetyltransferase that regulates the expression of multiple genes and is essential for human growth and development. METHODS: We identified a novel frameshift variant c.3185del (p.leu1062Argfs*52) in a 5‐year‐old Chinese boy and further analyzed KAT6B expression and its interacting complexes and downstream products using real‐time quantitative polymerase chain reaction (qPCR). Furthermore, we assessed its three‐dimensional protein structure and compared the variant with other reported KAT6B variants. RESULTS: The deletion changed the leucine at position 1062 into an arginine, resulting in translation termination after base 3340, which may have affected protein stability and protein–protein interactions. KAT6B mRNA expression levels in this case were substantially different from those of the parents and controls in the same age range. There were also significant differences in mRNA expression levels among affected children's parents. RUNX2 and NR5A1, downstream products of the gene, affect the corresponding clinical symptoms. The mRNA expression levels of the two in children were lower than those of their parents and controls in the same age range. CONCLUSION: This deletion in KAT6B may affect protein function and cause corresponding clinical symptoms through interactions with key complexes and downstream products.