Epilepsy in KAT6A syndrome: Description of two individuals and revision of the literature

Troisi, Serena; Maitz, Silvia; Severino, Mariasavina; Spano, Alice; Cappuccio, Gerarda; Brunetti‐Pierri, Nicola; Torella, Annalaura; Nigro, Vincenzo; Tudp,; Bilo, Leonilda; Coppola, Antonietta

doi:10.1016/j.ejmg.2021.104380

Cited by 6 publications

(7 citation statements)

References 13 publications

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“…Acute leukemias derived from oncogenic MOZ/MORF translocations and aberrant acetyltransferase activities are associated with poor prognosis and grim survival rates, prompting and accelerating the development of inhibitors for MOZ/MORF with several already showing promising results as anti-cancer therapeutics 15,16 . Pathogenic MOZ/ MORF have also been linked to developmental disorders, epilepsy, and intellectual disability [17][18][19][20] .…”

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confidence: 99%

MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain

et al. 2023

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Human acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the function of which remains unclear. Here, we identified and characterized two structured winged helix (WH) domains, WH1 and WH2, in MORF and MOZ. WHs bind DNA in a cooperative manner, with WH1 specifically recognizing unmethylated CpG sequences. Structural and genomic analyses show that the DNA binding function of WHs targets MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation, and WH1 recruits oncogenic fusions to HOXA genes that trigger leukemogenesis. Cryo-EM, NMR, mass spectrometry and mutagenesis studies provide mechanistic insight into the DNA-binding mechanism, which includes the association of WH1 with the CpG-containing linker DNA and binding of WH2 to the dyad of the nucleosome. The discovery of WHs in MORF and MOZ and their DNA binding functions could open an avenue in developing therapeutics to treat diseases associated with aberrant MOZ/MORF acetyltransferase activities.

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confidence: 99%

MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain

et al. 2023

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“…In the current case, there were typical features of KAT6A syndrome that included feeding difficulties, intellectual disability, microcephaly, hypotonia, language and developmental delay. 9,11,12,14 However, there was no evidence of epilepsy, eye features, sleep disturbances, gastrointestinal problems, haematological and immunological disturbances. 9,13 The most common clinical features of KAT6 syndrome are intellectual disability, speech delay and behavioural problems.…”

Section: Discussionmentioning

confidence: 98%

“…Since KAT6A is an acetylated epigenetic modifier, different variants have different phenotypes in different genetic backgrounds. 1 , 9 , 11 , 13 – 16 The mechanism of how the p.R1024X mutation leads to ASD and other phenotypes through an epigenetic mechanism needs to be studied further.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] Different variants of KAT6A syndrome present with different phenotypes such as congenital heart disease, behaviour, immunity and sleep disturbances. 1,9,11,[13][14][15][16] This current case report describes a Chinese boy with a nonsense mutation in the KAT6A gene. In addition to the common phenotypes such as intellectual disability, oromotor dyspraxia and language developmental delay, he also had atrial septal defect (ASD).…”

Section: Introductionmentioning

confidence: 88%

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The clinical spectrum of a nonsense mutation in KAT6A: a case report

Wang

et al. 2022

J Int Med Res

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KAT6A syndrome is an autosomal dominant genetic disorder associated with intellectual disability due to mutations in the lysine acetyltransferase 6A ( KAT6A) gene. There are some differences in phenotype between KAT6A gene variants. This current case report describes a 1-month-old male infant that had a nonsense mutation in the KAT6A gene. Neither of his parents had the mutation. The proband had feeding difficulties and a physical examination revealed the following: moderate dysphagia, hypoplastic laryngeal cartilage, poor audio-visual response, poor head-up ability, no active grasping awareness, microcephaly, high arched palate and he was significantly behind other children of the same age. Echocardiography showed that the foramen ovale was not closed. He was diagnosed with atrial septal defect (ASD) when 2 years old. The patient received ASD repair at 32 months of age. Head colour Doppler ultrasonography and brain magnetic resonance imaging showed cysts in the right ventricle and choroid plexus, which returned to normal at 2 years of age. This current case demonstrates that immediate surgery should be considered in newborns with KAT6A syndrome presenting with a heart malformation. A new KAT6A syndrome phenotype is described in this current case report, which requires early diagnosis and treatment.

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“… 4 , 5 , 6 Aberrant functions of MOZ/MORF have also been associated with developmental and neurological disorders and intellectual disability. 7 , 8 , 9 …”

Section: Introductionmentioning

confidence: 99%

The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300

Becht,

Kanai,

Biswas

et al. 2024

iScience

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Epilepsy in KAT6A syndrome: Description of two individuals and revision of the literature

Cited by 6 publications

References 13 publications

MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain

MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain

The clinical spectrum of a nonsense mutation in KAT6A: a case report

The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300

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