Identification of alternative transcripts of NSD1 gene in Sotos Syndrome patients and healthy subjects

Conteduca, Giuseppina; Testa, Barbara; Baldo, Chiara; Arado, Alessia; Malacarne, Michela; Candiano, Giovanni; Garbarino, Andrea; Coviello, Domenico; Cantoni, Claudia

doi:10.1016/j.gene.2022.146970

Cited by 8 publications

(3 citation statements)

References 44 publications

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“…All genomic positions were reported according to the human genome assembly (GRCh37/hg19). PCR amplification was performed using primers specific for the different 23 NSD1 exons as previously described (Conteduca et al, 2023). Briefly, Purified PCR products were sequenced with the ABI Big Dye terminator sequencing kit (Applied Biosystems, Foster City, CA) on an ABI Prism 3730 automatic DNA sequence (Applied Biosystems, Foster City, CA).…”

Section: Methodsmentioning

confidence: 99%

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A longitudinal characterization of the adaptive and behavioral profile in Sotos syndrome

Siracusano,

Dante,

Sarnataro

et al. 2024

American J of Med Genetics Pt A

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Delineation of a developmental and behavioral trajectory is a key‐topic in the context of a genetic syndrome. Short‐ and long‐term implications concerning school outcome, independent living, and working opportunities are strictly linked to the cognitive and behavioral profile of an individual. For the first time, we present a longitudinal characterization of the adaptive and behavioral profile of a pediatric sample of 32 individuals with Sotos Syndrome (SoS) (18 males, 14 females; mean age 9.7 ± 4 years, eight carrying the NSD1 5q35 microdeletion and 24 with an intragenic mutation). We performed two clinical assessments: at baseline (T0) and at distance evaluation (T1) of adaptive and behavioral skills with a mean distance of 1.56 ± 0.95 years among timepoints. Our study reports a stability over the years—meant as lack of statistically significant clinical worsening or improvement—of both adaptive and behavioral skills investigated, regardless the level of Intellectual Quotient and chronological age at baseline. However, participants who did not discontinue intervention among T0 and T1, were characterized by a better clinical profile in terms of adaptive skills and behavioral profile at distance, emphasizing that uninterrupted intervention positively contributes to the developmental trajectory.

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Section: Methodsmentioning

confidence: 99%

Section: Genetic Analysesmentioning

confidence: 99%

A longitudinal characterization of the adaptive and behavioral profile in Sotos syndrome

Siracusano,

Dante,

Sarnataro

et al. 2024

American J of Med Genetics Pt A

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“…The past two decades have seen significant advancements in genetic technology with notable enhancements in the detection efficiency and classification accuracy of SOTOS-related variations [ 11 ]. While the genotype–phenotype correlation of SOTOS has been explored in a few studies [ 3 , 9 , 12 – 14 ], the consensus is that individuals carrying the 5q35 microdeletion have milder overgrowth but more severe intellectual disabilities than those with the intragenic NSD1 pathogenic variant [ 2 ]. However, several other symptoms lack well-established associations with specific variants, necessitating further investigation.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome

Ren,

Yue,

et al. 2024

BMC Med Genomics

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Objective Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. Design&Methods A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. Results All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604–176,639,249)×1, which encompassed the 5′-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. Conclusion This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.

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H3K36 methyltransferase SMYD2 affects cell proliferation and migration in Hirschsprung's disease by regulating METTL3

Hou,

Yang,

Wang

et al. 2024

Journal Cellular Physiology

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The pathogenesis of Hirschsprung's disease (HSCR) is complex. Recently, it has been found that histone modifications can alter genetic susceptibility and play important roles in the proliferation, differentiation and migration of neural crest cells. H3K36 methylation plays a significant role in gene transcriptional activation and expression, but its pathogenic mechanism in HSCR has not yet been studied. This study aimed to elucidate its role and molecular mechanism in HSCR. Western blot analysis, immunohistochemistry (IHC) and reverse transcription‐quantitative PCR (RT‒qPCR) were used to investigate H3K36 methylation and methyltransferase levels in dilated and stenotic colon tissue sections from children with. We confirm that SMYD2 is the primary cause of differential H3K36 methylation and influences cell proliferation and migration in HSCR. Subsequently, quantitative detection of m6A RNA methylation revealed that SMYD2 can alter m6A methylation levels. Western blot analysis, RT‐qPCR, co‐immunoprecipitation (co‐IP), and immunofluorescence colocalization were utilized to confirm that SMYD2 can regulate METTL3 expression and affect m6A methylation, affecting cell proliferation and migration. These results confirm that the H3K36 methyltransferase SMYD2 can affect cell proliferation and migration in Hirschsprung's disease by regulating METTL3. Our study suggested that H3K36 methylation plays an important role in HSCR, confirming that the methyltransferase SMYD2 can affect m6A methylation levels and intestinal nervous system development by regulating METTL3 expression.

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Identification of alternative transcripts of NSD1 gene in Sotos Syndrome patients and healthy subjects

Cited by 8 publications

References 44 publications

A longitudinal characterization of the adaptive and behavioral profile in Sotos syndrome

A longitudinal characterization of the adaptive and behavioral profile in Sotos syndrome

Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome

H3K36 methyltransferase SMYD2 affects cell proliferation and migration in Hirschsprung's disease by regulating METTL3

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