Publications by authors named "G W E Santen"

Osteogenesis imperfecta (OI) is a rare disease, hallmarked by bone fragility, multiple fractures, and deformities, and is commonly caused by pathogenic variants in the genes encoding type I collagen. Type II OI is the most severe form and is lethal in the perinatal period. Here, we report recurrence of perinatal lethal OI in two fetuses due to parental mosaicism for a deep intronic pathogenic variant at c.

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Purpose: is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with -related disorder have been described, which limits our understanding of the disease's natural history and our ability to counsel patients and their families.

Methods: Data on patients aged 18+ years with -related disorder were collected through an online questionnaire completed by clinicians and parents.

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Article Synopsis
  • ARID1A and ARID1B duplications are linked to Coffin-Siris syndrome, but ARID1B duplications have not been previously associated with a specific clinical phenotype until now.
  • A study analyzed 16 cases of ARID1A and 13 cases of ARID1B duplications, revealing that ARID1A duplications resulted in more severe symptoms, including intellectual disabilities and growth delays, while both groups displayed similar features.
  • The research identified unique DNA methylation patterns in ARID1A duplication patients, which differ from those with loss-of-function variants, suggesting the presence of a distinct clinical phenotype for both ARID1A and ARID1B duplications, indicating a new type of
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Article Synopsis
  • The study highlights the role of the BAF chromatin remodeler, specifically the ARID1A subunit, in cranial neural crest cell (CNCC) specification and its link to Coffin-Siris syndrome (CSS).
  • ARID1A haploinsufficiency disrupts the epithelial-to-mesenchymal transition (EMT) vital for CNCC migration, while ARID1A-BAF regulates enhancers connected to EMT genes, demonstrating that ZIC2 binding at these enhancers relies on ARID1A.
  • The research establishes an important connection between ARID1A and ZIC2 in promoting EMT and successful CNCC delamination, suggesting implications for understanding congenital disorders like CSS.
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The shift to a genotype-first approach in genetic diagnostics has revolutionized our understanding of neurodevelopmental disorders, expanding both their molecular and phenotypic spectra. Kleefstra syndrome (KLEFS1) is caused by EHMT1 haploinsufficiency and exhibits broad clinical manifestations. EHMT1 encodes euchromatic histone methyltransferase-1-a pivotal component of the epigenetic machinery.

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