The factors that predispose individuals with Lynch syndrome to gastric cancer are not well-described. In our cohort of 255 individuals with Lynch syndrome, chronic immune gastritis was observed in over 70% of the cases with gastric cancer and in none of the patients without gastric cancer. This suggests that chronic inflammation is an important risk […]
Latest articles
Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility
Male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) is a genetically heterogeneous disorder. Previous studies revealed several MMAF-associated genes, which account for approximately 60% of human MMAF cases. The pathogenic mechanisms of MMAF remain to be illuminated. In this study, we identified SPEF2 as a novel gene for human MMAF across […]
Prenatal ultrasound findings of rasopathies in a cohort of 424 fetuses: update on genetic testing in the NGS era
In this study we describe the prenatal characteristics of Noonan syndrome and its associated syndromes called Rasopathies in 40 fetuses with a pathogenic variant in one of the Rasopathy genes. The most common feature is increased nuchal translucency (NT). Based on our data we suggest genetic testing of fetuses with an isolated persistent NT ≥5.0 […]
Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis
Congenital scoliosis (CS) is a common spinal anomaly and spondylo-costal dysostosis (SCDO) is a rare skeletal dysplasia affecting spine and rib. They have been considered to belong to different disease entities. We examined TBX6 in CS and SCDO and found loss-of-function (LOF) mutations in both. There were two LOF mechanisms: decreased transcriptional activity and mis-localization […]
Deciphering the complexity of the 4q and 10q subtelomeres by molecular combing in healthy individuals and patients with facio-scapulo-humeral dystrophy
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 […]
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% […]