Publications by authors named "A Allworth"
Article Synopsis
- - A rare genetic condition involving mitochondrial complex III deficiency and lactic acidosis, characterized by scalp alopecia, was identified in two unrelated cases and discussed further with a participant from the Undiagnosed Diseases Network (UDN).
- - The participant had two autosomal recessive disorders discovered through genome sequencing: mitochondrial complex III deficiency and cataracts, with specifics on previously documented pathogenic variants for each condition.
- - A combination of enzyme assays and cellular proteomics showed clear dysfunction in complex III and low levels of a crucial protein, validating the genetic mutations' pathogenic effects and broadening understanding of these rare disorders.
Article Synopsis
- DNA replication is crucial for cell division and maintaining genetic stability, with the RFC complex playing a key role by loading important proteins onto DNA.
- While RFC1's involvement in certain disorders is recognized, the impact of RFC2-5 subunits, particularly RFC4, on human genetic diseases remains under-researched.
- Our study identifies harmful variants in RFC4 linked to a new disorder marked by muscle weakness and hearing issues, showing how these variants disrupt RFC complex formation and ultimately affect DNA replication and cell cycle processes.
Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol, important signaling molecules involved in many cellular processes. encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of are observed in multiple cancers, but only one germline variant has been reported.
View Article and Find Full Text PDFResolving the molecular basis of a Mendelian condition (MC) remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome, and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion, and structural variant calling and diploid genome assembly, and permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility, and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network (UDN) participant with a chromosome X;13 balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (, , , and ) previously associated with single-gene MCs.
View Article and Find Full Text PDFObjectives: Transcript sequencing of patient-derived samples has been shown to improve the diagnostic yield for solving cases of suspected Mendelian conditions, yet the added benefit of full-length long-read transcript sequencing is largely unexplored.
Methods: We applied short-read and full-length transcript sequencing and mitochondrial functional studies to a patient-derived fibroblast cell line from an individual with neuropathy that previously lacked a molecular diagnosis.
Results: We identified an intronic homozygous c.