Vitamin A plays a crucial role in both eye development during pregnancy and function in adulthood. Mutations in the gene encoding its blood transporter, named RBP4, have been associated with two rare conditions: recessive degeneration of retina and dominant malformations of ocular globe. We report here 7 new families (13 individuals) with eye malformations caused […]
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Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project
In some inherited conditions, both copies of a gene must be altered (“variant”) to cause symptoms; these are known as autosomal recessive disorders. Some patients with suspected autosomal recessive disorders were recruited for whole genome sequencing (WGS) through the 100,000 Genomes Project after only one causative variant was detected. Clinical testing may not detect some […]
Germline HPF1 retrogene insertion in RB1 gene involved in cancer predisposition
About half of the human genome is composed of repeated sequences derived from mobile elements, generally without pathogenic effect. These include retrogenes, which derive from mRNAs retrotransposed into the genome and may encode functional proteins. Transposition of mobile elements are important elements involved in the evolution of species. Germline pathogenic variants in RB1 gene confer […]
CHEK2 is not a Li-Fraumeni syndrome gene: time to update public resources
CHEK2 is a moderate risk cancer predisposition gene, but is currently listed as “Li-Fraumeni syndrome 2” in public resources used by medical geneticists and patients. Li-Fraumeni syndrome experts consider that TP53 is the only gene causing this multi-cancer syndrome. Our comprehensive comparison of phenotypic characteristics of CHEK2 and TP53 carriers undergoing multigene panel testing provides conclusive evidence that none of the phenotypes significantly associated with TP53, including extremely early onset […]
Prevalence and clinical implications of germline pathogenic variants in cancer predisposing genes in young patients across sarcoma subtypes
Sarcomas are a group of rare cancers that mainly affect young people. We aimed to understand the genetic causes of sarcomas by analyzing a group of genes in 177 Brazilian children, adolescents, and young adults with sarcomas. We showed that 21.5% of these patients had harmful genetic variants that could raise the risk of developing […]
Integrating RNA-Seq into genome sequencing workflow enhances the analysis of structural variants causing neurodevelopmental disorders
Genetic testing plays a crucial role in diagnosing neurodevelopmental disorders (NDD). Geneticists continuously explore new methods, such as genome sequencing (GS), to improve diagnostic accuracy. However, some genetic variations detected by GS are challenging to understand. To address this, we combined GS with RNA-Seq, a technique that provides extra information about how these variations affect […]
Clinical phenotype and genetic function analysis of a rare family with hereditary leiomyomatosis and renal cell carcinoma complicated with Birt–Hogg–Dubé syndrome
Hereditary renal cell carcinoma (RCC) accounts for 5% of renal cancers and is mostly autosomal dominant inheritance. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and Birt–Hogg–Dube (BHD) syndromes are caused by mutations in the fumarate hydratase (FH) and folliculin (FLCN) genes, respectively. Over 200 families with HLRCC and over 600 families with BHD have been […]
Performance of the eHealth decision support tool, MIPOGG, for recognising children with Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin syndromes
Cancer predisposition syndromes (CPSs) are genetic conditions that increase the risk of developing cancer throughout life. It is sometimes difficult for doctors to recognize various types of CPSs in their patients. Recently, an app called MIPOGG was created to help clinicians identify which of their pediatric cancer patients could have a CPS. In this study, […]
Exome sequencing links the SUMO protease SENP7 with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia
SUMOylation is a type of protein modification occurring in the cell. It includes the attachment of Small Ubiquitin-like Modifier (SUMO) to large sets of proteins to regulate their function. Abnormalities in protein SUMOylation are linked with various disease states, however, knowledge of the specific roles of the SUMOylation machinery in human disease is limited. In […]
Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel
Large-scale genetic studies conducted over the last decade discovered dozens of genetic variants that are associated with increased risk for breast cancer (BC). These BC-risk variants can be used to calculate a genetic risk score (called ‘polygenic risk score’ – PRS) which has the predictive capacity to detect women with significantly elevated genetic risk for […]