Molecular diagnostics of FSHD remains complex for approximately 20% of patients, posing difficulties in genetic counseling. To overcome these current limitations, we have developed a molecular combing-based method allowing a precise bar coding of the 4q35 locus linked to the disease and 10qter region, which is highly homologous. By exploring a thousand cases with this […]
Latest articles
Mutation-specific Fabry disease patient-derived cell model to evaluate the amenability to chaperone therapy
Patients with Fabry disease (FD) and amenable mutations can be treated with the chaperone migalastat to restore endogenous α-galactosidase A (AGAL) activity. Our study demonstrates that repeated AGAL activity measurements in patients’ white blood cells at treatment-naïve baseline and during follow-up is mandatory to assess the in vivo amenability to migalastat. In addition, plasma lyso-globotriaosylceramide […]
Functional analysis of novel desert hedgehog gene variants improves the clinical interpretation of genomic data and provides a more accurate diagnosis for patients with 46,XY differences of sex development
Babies can sometimes be born with atypical reproductive organs or external genitalia – these conditions are called Differences/Disorders of Sex Development (DSD). In some cases, if the genetic cause is unknown, doctors can be left guessing as to the best treatment. Changes in the Desert Hedgehog (DHH) gene can result in DSD, although this is […]
A novel mutation in the GFAP gene expands the phenotype of Alexander disease
We used exome sequencing to diagnose a family presenting with adult-onset spastic paraplegia. We identified a novel variant in GFAP (p.Gly18Val) cosegregating in multiple relatives, reaching a LOD score of 2.7. All patients showed characteristic signal changes in MRI and abnormal MRS. In vitro, this variant did not cause significant protein aggregation, but enlarged size of astrocytes instead, consistent […]
Multivariate genome-wide association study of rapid automatized naming and rapid alternating stimulus in Hispanic American and African American youth
Rapid automatized naming (RAN) and rapid alternating stimulus (RAS) are measures that involve naming familiar items quickly and accurately. They are also reliable predictors of dyslexia. The high correlations between RAN, RAS, and reading could be due to genetic factors that they share in common, and that modify an underlying biological mechanism. We describe genetic […]
Resectable Lung Lesions Malignancy Assessment and Cancer Detection by Ultra-Deep Sequencing of Targeted Gene Mutations in Plasma Cell-Free DNA
Liquid biopsy detecting circulating tumor DNA in the blood is promising in non-invasively providing valuable molecular information on the small nodules found on the low dose CT images. In a cohort of 192 patients with nodules sized between 0.5 – 3 cm and diagnosed by pathology to be one quarter of benign disease and 85% […]
Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: Results of the observational AGO-TR1 study
For individuals with ovarian cancer, therapy options mainly depend on BRCA1/2 germline status. As part of the observational AGO-TR1 study (NCT02222883), we conducted a paired blood/tumor analysis of 473 patients with ovarian cancer. Deleterious germline variants were found in 26.4% of the individuals, including BRCA1 and BRCA2. Tumor sequencing of the BRCA1, BRCA2, PIK3CA and […]
Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report
The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA – https://enigmaconsortium.org/) is a global research active consortium in which members have expertise in developing and bringing together a robust evidence base to underpin robust clinical utilization of inherited variants in breast and ovarian cancer susceptibility genes. The consortium was created a decade ago […]
Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders
Balanced chromosomal rearrangements associated with intellectual disability and / or malformations are rare events but are still challenging for genetic counselling since breakpoints characterisation is not performed routinely. We used whole genome sequencing to characterise the breakpoints of chromosomal rearrangements in 55 patients with ID/M. We were able to identify the rearrangement in 49/55 patients […]
Genetic linkage analysis of a large family identifies FIGN as a candidate modulator of reduced penetrance in heritable pulmonary arterial hypertension
The penetrance of a genetic disorder is the risk for disease onset, given the disease-causing mutation. Heritable pulmonary arterial hypertension (PAH) is a rare genetic disorder characterised by mutations mostly occurring in the bone morphogenetic protein receptor type 2 (BMPR2) gene, and a wide heterogeneity of penetrance modifier mechanisms. In this study, we genotyped 32 […]