Publications by authors named "J Chrast"
Article Synopsis
- The KINSSHIP syndrome, caused by de novo variants in the AFF3 gene, leads to intellectual disability, mesomelic dysplasia, and horseshoe kidneys, and is characterized by a dominant-negative effect from increased levels of AFF3.
- Researchers screened intellectual disability cohorts and used animal models to explore additional inheritance patterns and found a range of variants in AFF3, including a de novo duplication linked to a severe phenotype and variants that caused milder symptoms.
- Analysis of zebrafish models confirmed the pathogenic effects of specific AFF3 variations, showing that some mutations disrupted normal function while others led to more severe conditions in individuals with homozygous or compound heterozygous variants.
Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,caused by variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative (DN) mode-of-action, wherein an increased level of AFF3 resulted in pathological effects.
Methods: Evolutionary constraints suggest that other mode-of-inheritance could be at play.
Article Synopsis
- Recurrent copy-number variations (CNVs) at chromosome 16p11.2 are linked to various health issues like neurodevelopmental disorders, anemia, and immune system problems, particularly impacting genes related to leukocyte function.
- In a study of 32 families, three deletion carriers exhibited conditions like neutropenia and lymphopenia, suggesting that the CNV might be a contributing factor, especially due to their low levels of the BOLA2 gene.
- Research also indicated that individuals with 16p11.2 deletions had distinct blood cell counts, with lower lymphocytes and higher neutrophils, pointing to the need for more extensive studies to understand the relationships between these CNVs, gene expressions, and their health
Non-Syndromic Hereditary Hearing Loss (NSHHL) is a genetically heterogeneous sensory disorder with about 120 genes already associated. Through exome sequencing (ES) and data aggregation, we identified a family with six affected individuals and one unrelated NSHHL patient with predicted-to-be deleterious missense variants in USP48. We also uncovered an eighth patient presenting unilateral cochlear nerve aplasia and a de novo splice variant in the same gene.
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