Publications by authors named "A Begtrup"
De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation.
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- The ongoing GUARDIAN study aims to evaluate the feasibility and acceptability of genome sequencing as an addition to traditional newborn screening across diverse racial and ethnic groups in New York City.
- As of the interim analysis covering 4,000 newborns, 72% of approached families consented to participate, reflecting a representative sample of various racial and ethnic demographics.
- The study primarily assessed the screen-positive rate, enrollment rate, and successful sequencing completion, with a large majority of families opting to screen for both early-onset genetic conditions and additional neurodevelopmental disorders.
Purpose: Research is underway worldwide to investigate the feasibility, acceptability, and utility of sequencing-based newborn screening. Different methods have been used to select gene-condition pairs for screening, leading to highly inconsistent gene lists across studies.
Methods: Early Check developed and utilized actionability-based frameworks for evaluating gene-condition pairs for inclusion in newborn panels (panel 1-high actionability, panel 2-possible actionability).
Article Synopsis
- FLVCR1 is a protein involved in transporting essential compounds like heme and choline, with mutations linked to serious developmental disorders and neurodegenerative conditions in humans.
- Researchers identified 30 patients with biallelic FLVCR1 variants who displayed severe developmental issues, including brain malformations and other complications, paralleling symptoms seen in mouse models and conditions like Diamond-Blackfan anemia (DBA).
- The findings emphasize that FLVCR1 variants could cause a wide range of health problems, underscoring the need for diverse genetic testing and consideration of animal model data in understanding human genetic disorders.
Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.
Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.