Genetic diagnostic laboratories classify DNA sequence variants based on available evidence, following guidelines for variant interpretation. Despite guidelines, laboratories may differ in how they classify the same variant, for example because of differences in how they apply the interpretation criteria. The Canadian Open Genetics Repository (COGR) is an online collaborative effort for data sharing and […]
Latest articles
Adult phenotype of KCNQ2 encephalopathy
In this study, we describe the disease evolution and adult phenotype of KCNQ2 encephalopathy through retrospective study of 13 patients (18-45 years of age). We show that seizure frequency declines over the years and that most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are however common during childhood and adolescence. […]
Mutations in Phospholipase C eta-1 (PLCH1) are associated with Holoprosencephaly
Holoprosencephaly is a rare neurodevelopmental syndrome in which the brain doesn’t properly divide into the right and the left hemispheres. The condition can be caused by mutations in different genes. Our study descrides two families in which offspring had holoprosencephaly with mutations in a new gene called phospholipase C eta-1 (PLCH1). In the physiological condition, […]
Clinical and subclinical findings in heterozygous ABCC6 carriers: results from a Belgian cohort and clinical practice guidelines
Hereditary defects in the ABCC6 gene are common in the general population with an estimated 1% of individuals having such a defect in their genetic material. In this study, we examined the physical signs and symptoms in a group of 56 individuals having 1 ABCC6 defect, called ‘carriers’. We found that 24% of carriers have […]
Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore
Pathogenic variants in PALB2 is associated with an increased risk of breast, ovarian and pancreatic cancer. In our case-control study of more than 15,000 women from two multi-ethnic South East Asian populations (Malaysia and Singapore), we found that PALB2 carriers have a 5 fold increased risk of breast cancer compared to healthy individuals. Notably, many of the variants identified in this […]
High cumulative risk of colorectal cancers and desmoid tumours and fibromatosis in South Asian APC mutation carriers
Familial Adenomatous Polyposis (FAP) is a rare inherited syndrome due to APC gene mutation. The extensive colorectal polyps and cancer risk requires lifelong endoscopic surveillance, often with preventive colorectal surgery before cancer development. FAP manifestation depend on the location of APC mutation which could vary in different populations. We report several novel mutations and a […]
High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer
Women diagnosed with breast cancer at a very early age (≤30 years) are more likely to have a genetic predisposition. Pathogenic variants in BRCA1, BRCA2 and TP53 are often associated with an early onset of disease. However, the association is unclear for other breast cancer associated genes. Here, we assessed the contribution of pathogenic variants […]
Rising of LOXHD1 as a signature causative gene of down-sloping hearing loss in people in their teens and twenties
Down-sloping sensorineural hearing loss is an easy-to-overlook issue for its significance. However, it can hamper efficient communication and in-depth social interaction, and learning ability is severely damaged especially in people in their teens and twenties. Even people with the disease usually don’t seek for medical advice or supportive devices because converstion might be possible in […]
Refining the mutational spectrum and gene-phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study
Pontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders profoundly impacting on child neurodevelopment. Genotype-phenotype associations are still limited, with negative consequences on prognosis and counselling. Here, we provide a comprehensive and systematic phenotypic assessment of 56 PCH patients with different genetic etiology. We identified three major PCH genes and investigated their association with […]
Genetic variants associated with expression of TCF19 contribute to the risk of head and neck cancer in Chinese population
Our study identified a novel functional variant rs3094187 associated with SCCHN risk, which could modify TCF19 expression by regulating the binding affinity of the transcription factor SREBF1. Further functional investigations demonstrated that TCF19 was overexpressed in SCCHN and the inhibition of TCF19 might attenuate the proliferation and migration of SCCHN cell lines, as well as […]