Clinical features and underlying mechanisms of <scp>KAT6B</scp> disease in a Chinese boy

Sun, Xiaoang; Luo, Xiaona; Lin, Lei; Wang, Simei; Wang, Chunmei; Fang, Yuan; Lan, Xiaoping; Yan, Jingbin; Chen, Yucai

doi:10.1002/mgg3.2202

Cited by 2 publications

(1 citation statement)

References 39 publications

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“…Additionally, we provided an assessment of KAT6B mRNA abundance and histone acetyltransferase function for a range of KAT6B variants in human cells. Our observation that KAT6B mRNA levels were reduced in cells with all SBBYSS mutations except for those in the final exon 18 is congruent with previous assessments of 2 proximal KAT6B mutations ( 26 , 27 ) and 4 mutations in the final exon ( 27 ), together suggesting that KAT6B variants outside the final exon undergo nonsense-mediated decay. In the absence of reliable antibodies against KAT6B, we cannot verify whether abnormal KAT6B protein is produced in our KAT6B mutant HEK293T cell lines.…”

Section: Discussionsupporting

confidence: 91%

Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice

Bergamasco,

Vanyai,

Garnham

et al. 2024

Journal of Clinical Investigation

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Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease. Here, we provide a mouse model of Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736) and demonstrate proof-of-principle efficacy of postnatal treatment. SBBYSS results from heterozygous mutations in the KAT6B ( MYST4/MORF/QFK ) gene and is characterized by intellectual disability and autism-like behaviors. Using human cells carrying SBBYSS-specific KAT6B mutations and Kat6b heterozygous mice ( Kat6b +/– ), we showed that KAT6B deficiency caused a reduction in histone H3 lysine 9 acetylation. Kat6b +/– mice displayed learning, memory, and social deficits, mirroring SBBYSS individuals. Treatment with a histone deacetylase inhibitor, valproic acid, or an acetyl donor, acetyl-carnitine (ALCAR), elevated histone acetylation levels in the human cells with SBBYSS mutations and in brain and blood cells of Kat6b +/– mice and partially reversed gene expression changes in Kat6b +/– cortical neurons. Both compounds improved sociability in Kat6b +/– mice, and ALCAR treatment restored learning and memory. These data suggest that a subset of SBBYSS individuals may benefit from postnatal therapeutic interventions.

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Section: Discussionsupporting

confidence: 91%

Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice

Bergamasco,

Vanyai,

Garnham

et al. 2024

Journal of Clinical Investigation

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De novo KAT6B mutation causes Say–Barber–Biesecker–Young–Simpson variant of Ohdo syndrome in an Iranian boy: a case report

Davarnia,

Panahi,

Rahimi

et al. 2024

J Med Case Reports

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Background Say–Barber–Biesecker–Young–Simpson (SBBYS) (OMIM #603736, Ohdo syndrome variant) is a rare type of severe blepharophimosis intellectual disability syndrome, which is generally characterized by a global developmental delay, distinctive facial features, and intellectual disability with multiple congenital anomalies, including skeletal involvement, missing, or underdeveloped kneecaps, and genital anomalies, in affected males. It has been shown that mutations in the KAT6B gene, which is a lysine acetyltransferase-encoding gene, have been associated with SBBYS syndrome. All the known variants are dominant de novo mutations that result in protein truncation. Case presentation A 14-year-old Iranian Azeri boy with an intellectual disability, distinct dysmorphic facial features such as open-mouth expression, sparse medial eyebrows, widely spaced upward-slanted eyes, epicanthal folds, broad nasal bridge, low-set ears, anteverted ears, short philtrum, hypertelorism, microphthalmia is presented in this case study. Cryptorchidism was reported. Neurologically, the patient presented with poor eye contact, hypotonia, and speech difficulties. In the skeletal X-ray, underdeveloped kneecaps with some new features were observed. Conclusion We present the first case of SBBYS syndrome in association with some new anomaly features in the Iranian population. Based on this diagnosis, we could provide the patient with a suitable plan of management as well as appropriate genetic counseling for his family.

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

Cited by 2 publications

References 39 publications

Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice

Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice

De novo KAT6B mutation causes Say–Barber–Biesecker–Young–Simpson variant of Ohdo syndrome in an Iranian boy: a case report

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