Cerebrovascular diseases in two patients with entire NSD1 deletion

Itai, Toshiyuki; Miyatake, Satoko; Hatano, Taku; Ohno, Akihiko; Aoki, Yusuke; Itomi, Kazuya; Mori, Hiromu; Saitsu, Hirotomo; Matsumoto, Naomichi

doi:10.1038/s41439-021-00151-z

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…9 More recently, Itai et al reported a male with subdural hematoma and parenchymal hemorrhage in the posterior lobes in the neonatal period, as well as a 39-year-old woman with evidence of recurrent parenchymal hemorrhage. 10 Park et al additionally reported an infant with Sotos syndrome requiring a subduroperitoneal shunt at 10 months due to a severe subdural hygroma. 11 In addition to the above examples in the literature, the two cases presented herein suggest that some individuals with Sotos syndrome may be predisposed to SDH beginning in early infancy, possibly related to enlarged subdural spaces.…”

Section: Discussionmentioning

confidence: 99%

Subdural Hemorrhage as an Early Presentation in a Case of Sotos Syndrome

et al. 2023

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Subdural hemorrhages (SDH) in the pediatric population are associated with a high mortality and morbidity and may present in the context of abusive head trauma. Diagnostic investigations for such cases often include evaluation for rare genetic and metabolic disorders that can have associated SDH. Sotos syndrome is an overgrowth syndrome associated with macrocephaly and increased subarachnoid spaces and rarely with neurovascular complications. Here, we report two cases of Sotos syndrome, one with SDH during infancy who underwent repeated evaluation for suspected child abuse prior to the Sotos syndrome diagnosis, and the other with enlarged extra-axial CSF spaces, demonstrating a possible mechanism for SDH development in this setting. These cases suggest that some individuals with Sotos syndrome may be at elevated risk of developing SDH in infancy, and that Sotos syndrome should be on the differential diagnosis during a medical genetics evaluation in cases of unexplained SDH, especially in the setting of macrocephaly.

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Section: Discussionmentioning

confidence: 99%

Subdural Hemorrhage as an Early Presentation in a Case of Sotos Syndrome

et al. 2023

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“…Cells derived from a patient with Soto’s syndrome hosting an NSD1-inactivating mutation was shown to have a global redistribution of the DNA methyltransferase DNMT3A, along with promoter DNA hypomethylation, dysregulated synapse formation, and dysregulated neurodevelopmental gene expression [ 129 – 131 ]. Moreover, individuals hosting NSD1 whole-gene deletions exhibited early-onset cerebrovascular diseases [ 132 ]. This phenotype was recapitulated by deletion of an NSD1 -like gene in fly, with developmental symptoms accompanied by global H3K36me2 reduction, defective motor and memory functions, and body size overgrowth [ 133 ].…”

Section: Histone H3k36 Di-methyl Transferasesmentioning

confidence: 99%

Structural and functional specificity of H3K36 methylation

Lam

Tan

Poh

et al. 2022

Epigenetics & Chromatin

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The methylation of histone H3 at lysine 36 (H3K36me) is essential for maintaining genomic stability. Indeed, this methylation mark is essential for proper transcription, recombination, and DNA damage response. Loss- and gain-of-function mutations in H3K36 methyltransferases are closely linked to human developmental disorders and various cancers. Structural analyses suggest that nucleosomal components such as the linker DNA and a hydrophobic patch constituted by histone H2A and H3 are likely determinants of H3K36 methylation in addition to the histone H3 tail, which encompasses H3K36 and the catalytic SET domain. Interaction of H3K36 methyltransferases with the nucleosome collaborates with regulation of their auto-inhibitory changes fine-tunes the precision of H3K36me in mediating dimethylation by NSD2 and NSD3 as well as trimethylation by Set2/SETD2. The identification of specific structural features and various cis-acting factors that bind to different forms of H3K36me, particularly the di-(H3K36me2) and tri-(H3K36me3) methylated forms of H3K36, have highlighted the intricacy of H3K36me functional significance. Here, we consolidate these findings and offer structural insight to the regulation of H3K36me2 to H3K36me3 conversion. We also discuss the mechanisms that underlie the cooperation between H3K36me and other chromatin modifications (in particular, H3K27me3, H3 acetylation, DNA methylation and N6-methyladenosine in RNAs) in the physiological regulation of the epigenomic functions of chromatin.

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Cerebrovascular diseases in two patients with entire NSD1 deletion

Cited by 2 publications

References 10 publications

Subdural Hemorrhage as an Early Presentation in a Case of Sotos Syndrome

Subdural Hemorrhage as an Early Presentation in a Case of Sotos Syndrome

Structural and functional specificity of H3K36 methylation

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