Publications by authors named "Sarah Josephi-Taylor"
Article Synopsis
- This study identifies a new type of autosomal recessive intellectual disability linked to genetic variants in the GTF3C3 gene, which is essential for proper RNA polymerase III activity.
- Researchers employed various methods, including exome sequencing and Drosophila models, to analyze the effects of GTF3C3 variants found in twelve affected individuals from seven families.
- The results showed that the variants lead to significant functional losses in the gene, correlating with symptoms like intellectual disability, motor issues, seizures, and brain structure abnormalities.
Article Synopsis
- KMT2C and KMT2D are important enzymes that modify genes, with KMT2C haploinsufficiency recently linked to Kleefstra syndrome 2, a neurodevelopmental disorder (NDD) with unknown clinical details.
- A study involving 98 individuals found that most pathogenic variants in KMT2C span nearly all its exons, making variant interpretation difficult; the study also established a KMT2C DNA methylation signature for better classification of the disorder.
- Key features of KMT2C-related NDD include developmental delays, intellectual disabilities, and distinct facial characteristics, setting it apart from similar conditions like Kleefstra and Kabuki syndromes, indicating the need for its renaming and
Aim: Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue.
View Article and Find Full Text PDFProtocol for a comprehensive prospective cohort study of trio-based whole-genome sequencing for underlying cancer predisposition in paediatric and adolescent patients newly diagnosed with cancer: the PREDICT study.
BMJ Open
May 2023
Introduction: Identifying an underlying germline cancer predisposition (CP) in a child with cancer has potentially significant implications for both the child and biological relatives. Cohort studies indicate that 10%-15% of paediatric cancer patients carry germline pathogenic or likely pathogenic variants in cancer predisposition genes, but many of these patients do not meet current clinical criteria for genetic testing. This suggests broad tumour agnostic germline testing may benefit paediatric cancer patients.
View Article and Find Full Text PDFArticle Synopsis
- De novo variants contribute significantly to neurodevelopmental disorders (NDDs), but due to their rarity, understanding the full range of symptoms and genetic variations linked to specific genes like KDM6B poses a challenge.
- The study of 85 individuals with KDM6B variants reveals that cognitive deficits are common, while features like coarse facies and skeletal issues are rare, indicating that existing descriptions may be misleading.
- Through innovative testing methods and studies on Drosophila, the researchers highlight the critical role of KDM6B in cognitive function and the importance of international collaboration for accurate diagnosis of rare disorders.
Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy).
Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases.
The study aimed to explore with consanguineous couples in Australia the acceptability and perceived utility of whole exome reproductive carrier screening for autosomal recessive and X-linked recessive conditions. Semi-structured interviews with 21 consanguineous couples were conducted prior to the offer of screening. Interviews were coded, and thematic analysis was informed by an inductive approach.
View Article and Find Full Text PDFPurpose: To provide proof of concept by broadening preconception screening beyond targeted testing to inform reproductive risk in consanguineous couples.
Methods: Consanguineous couples were screened for autosomal recessive and X-linked disorders using the TruSight One panel of 4,813 genes associated with human disease.
Results: We recruited 22 couples, of whom 15 elected to have sequencing.