We report a 52 year old Caucasian male with a referring diagnosis of neurofibromatosis type 1 (NF1), due to multiple nerve sheath tumors, who was subsequently found to have a large deletion spanning CDKN2A,the major melanoma susceptibility gene, and including approximately 24 additional genes underlying his strong family history of melanoma and neural system tumors. […]
HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer
Every colorectal cancer (CRC) patient should be tested for Microsatellite Instability (MSI), as a first screen for Lynch syndrome (LS). Recently, clinical benefit from immune checkpoint blockade was reported in metastatic MSI CRCs. Hence, there is a high level of interest in studying the MSI phenotype as a potential prognostic and predictive biomarker in CRC […]
Multigene testing of moderate-risk genes: be mindful of the missense
What fraction of early-onset breast cancer patients inherited a clinically actionable moderate-risk genotype? To estimate this, we applied both multi-gene mutation screening and SNP genotyping to 1,297 early onset breast cancer cases and 1,121 controls. Mutation screening revealed that 2.1% of the cases carried an obviously pathogenic protein-truncating variant in one of nine moderate-risk genes, […]
Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy
Mitochondria, “the powerhouses of the cells” are dynamic organelles which undergo continuous fission and fusion to maintain their diverse cellular functions. Mitochondrial fission factor MFF is a component of the fission machinery shared between mitochondria and peroxisomes. We for the first time present detailed clinical and functional data of three patients with loss of function […]
Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects
Laminins are proteins that form a major component of basement membranes and extracellular matrix in human tissues. We have performed clinical and neuropsychiatric evaluation, and molecular analysis in patients with mutations in the LAMA1 gene that codes for the protein laminin-α1. We investigated the consequence of mutations in LAMA1 using nerve cells derived from stem […]
A Genetic Region Associated with Seizure Susceptibility is Identified in Wolf-Hischhorn Syndrome
Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the short arm of chromosome 4. Approximately 90% of individuals with WHS have seizures. These seizures can be intractable and can seriously affect an individual’s quality of life, especially during childhood. To study the genetic correlates of seizure susceptibility in […]
Identification of novel genetic causes of Rett syndrome-like phenotypes
Rett syndrome (RTT) is a severe neurodevelopmental disorder. We investigated a group of 19 MECP2 and CDKL5 negative RTT-like patients. Pathogenic genomic imbalances were found in two patients: a 18q21.2 deletion encompassing TCF4 and a mosaic uniparental disomy of chromosome 3. Very likely pathogenic sequence variants were identified through exome sequencing in genes previously implicated […]
Current needs for human and medical genomics research infrastructure in low and middle income countries
Researchers from Colombia, China, India, Mexico, South Africa, Australia, United States and Canada address “Current Needs for Human and Medical Genomics Research Infrastructure in Low and Middle Income Countries”. Due to the high costs of the needed research infrastructure, a large number of the human genomic centers around the globe are located in developed countries. […]
KCNT1 mutations in seizure disorders: the phenotypic spectrum and functional effects
Mutations in the potassium channel subunit gene KCNT1 have been identified during the past three years in patients with neurological disorders including nocturnal frontal lobe epilepsy, epileptic encephalopathies and white matter diseases. KCNT1 mutations have also been linked to cardiac arrhythmias. In this review we describe the current knowledge of the KCNT1 gene and its […]
Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia
Primary ciliary dyskinesia (PCD) is a genetic disorder that severely affects the quality of life, manifests early in life, and leads to premature death. PCD is characterized by dysfunction of motile cilia that causes progressive impairment of pulmonary function and severe respiratory infections. There is no specific cure. This study demonstrates that gene dysfunction causing […]