Short-read Genome sequencing (sr-GS) affords efficient characterization of apparently balanced chromosomal rearrangement. However, 9 to 11% of cases remain undetectable, mainly due to highly repetitive genomic regions at breakpoints. We studied 14 patients with abnormal phenotype carrying ABCR that could not be detected by sr-GS. We used a combination of different approaches including fluorescence in […]
Latest articles
Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort
Hereditary Hemorrhagic Telangiectasia (HHT) and Juvenile Polyposis Syndrome (JPS) can be caused by deleterious variants in the SMAD4 gene, which is part of the TGFß/BMP signaling pathway. We developed a functional assay for SMAD4 variants that allows discrimination between benign and pathogenic SMAD4 variants. We found that all the variants tested led to a loss of function in the SMAD4 protein. […]
First intragenic inversion of CYP11B1 gene causing 11β-hydroxylase deficiency: a molecular diagnosis easily overlooked
Steroid hormones are essential for the body to function properly. 11beta-hydroxylase deficiency is a rare genetic disorder that disrupts the production of steroid hormones. We have studied a patient with this deficiency and have identified a structural anomaly in the CYP11B1 gene in this family, which is particularly complicated to identify: the region of the […]
Homologous recombination deficiency in unselected high-grade ovarian carcinoma
1008 women with high-grade ovarian carcinoma (serous, endometrioid, clear cell, carcinosarcoma) were tested for pathogenic variants (PV) in germline homologous recombination repair (HRR) genes and tumour homologous recombination deficiency (HRD) including tumour BRCA1/2 and genomic instability (GI). Over 95% of tumours with a BRCA1 PV had High GI, whilst only 80% with a BRCA2 PV […]
New patients with duplication of the pituitary gland–plus syndrome, including a PTCH2 variant and a literature review
Duplication of the Pituitary Gland Plus Syndrome is an extremely rare condition, with fewer than 60 cases reported worldwide. It involves having two pituitary glands, abnormal neck bones, cleft palate, and a teratoma (benign tumor) inside the mouth at birth—features that suggest a genetic cause rather than occurring by chance. We report the first two […]
Exploration of possible association of BRIP1 pathogenic variants with central nervous system cancers in an institutional cohort
Our study examines a potential link between BRIP1 pathogenic germline variants (PGVs) and central nervous system (CNS) tumors through a retrospective review of institutional germline and somatic databases. We found that 16.3% of families with BRIP1 PGVs reported CNS tumors. Somatic BRIP1 variants were rare in CNS tumors, but one of two individuals subsequently germline […]
Refined genotype–phenotype correlations in neurofibromatosis type 1 patients with NF1 point variants
Neurofibromatosis type 1 (NF1) is a genetic condition that can cause a wide range of medical issues, with symptoms varying greatly between individuals. In this study, we analyzed over 100 patients with specific NF1 gene mutations and found that some of these variants are consistently associated with milder or more severe forms of the disease. […]
Congenital heart disease in 22q11.2 Deletion syndrome: meta-analysis and systematic review of the literature
22q11.2 deletion syndrome is recognized as the second most common genetic cause of congenital heart defects. While congenital heart abnormalities are common among individuals with 22q11.2 deletion syndrome, exact prevalence figures remain unclear. We conducted a meta-analysis of prevalence. Elevated prevalence rates were found for tetralogy of Fallot (20%) ventricular septal defect (14%) pulmonary atresia […]
Biallelic loss-of-function variants in C19orf44 lead to retinal degeneration
Inherited retinal diseases (IRDs) are genetic conditions that cause progressive vision loss. Many cases remain unsolved due to unidentified genetic causes. In this study, researchers used advanced genetic testing and eye imaging to investigate such cases and discovered diseasecausing variants in a previously unlinked gene, C19orf44. This gene has not been associated with any disease […]
‘Knowing and Treating Kosaki/Penttinen syndrome’ international collaborative consortium: recommendations for follow-up, natural history and a real-life observational study about safety and efficacy profile of tyrosine kinase inhibitors
Kosaki and Penttinen syndromes are extremely rare genetic conditions that cause serious problems in multiple organs, including the brain, bones, and blood vessels. Since 2019, an international team of doctors and researchers has been working together to better understand and treat these conditions. They have created shared care guidelines, a global patient database, and are […]