Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Sun X

PROVIDER: S-EPMC10496035 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Sun Xiaoang X Luo Xiaona X Lin Longlong L Wang Simei S Wang Chunmei C Yuan Fang F Lan Xiaoping X Yan Jingbin J Chen Yucai Y

Molecular genetics & genomic medicine 20230608 9

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 37288707

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Project description:BackgroundSay-Barber-Biesecker-Young-Simpson (SBBYSS) variant of Ohdo syndrome is a rare, autosomal dominant and clinically heterogenous disorder, caused by pathogenic variants in the KAT6B gene located on chromosome 10q22.2. KAT6B encodes a highly conserved histone acetyltransferase belonging to the MYST family. Currently, diseases caused by pathogenic variants in KAT6B (KAT6B-related disorders) comprise two allelic entities: SBBYSS variant of Ohdo syndrome and genitopatellar syndrome (GPS). Increase in the number of cases with overlapping GPS/SBBYSS phenotype which makes it necessary to redefine this group of phenotypes as KAT6B-related disorders or KAT6B spectrum disorders. Individuals with SBBYSS usually present with facial abnormalities, hypotonia, joint laxity, feeding problems, and long thumbs/great toes. This syndrome also typically involves skeletal problems including patellar hypoplasia/agenesis.MethodsHere we report six SBBYS syndrome patients with the same dysmorphic features but a different course of the disease. One known and five novel KATB6 pathogenic variants were identified by molecular diagnostics using Next Generation Sequencing (NGS).ResultsWe present a detailed phenotypic analysis of six individuals with KAT6B-related disorders, in whom a heterozygous pathogenic variant in KAT6B gene was found. In all of our patients facial dysmorphism as well as developmental and speech delay were present. Additionally, all but one patients presented with hypotonia, ocular abnormalities and long thumbs. Most of our probands showed blepharophimosis and skeletal (mainly knee) defects. Contrary to previously reported severe patellar defects (hypoplasia/agenesis) anomalies presented by our patients were less severe (dysplasia, habitual dislocation, subluxation) referring to KAT6B-related disorders.ConclusionWhile most of the anomalies found in our patients comply with SBBYSS criteria, phenotypic differences in our probands support a broader spectrum of the disease phenotype. To establish the range of this spectrum, a detailed analysis of clinical variability among patients with SBBYSS requires further investigation.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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