The HACE1 gene encodes a ubiquitin ligase involved in regulating several small GTPases. It has previously been proposed to be a tumour suppressor, whose function is impaired in various forms of cancer. In this study, Hollstein et al. have identified biallelic null HACE1 mutations in eight individuals from two families with an autosomal recessive syndrome […]
Latest articles
Zollino et al KANSL1 haploinsufficiency syndrome
Among rare diseases, the KANSL1 haploinsufficiency syndrome is one of the most common conditions. It can be caused by a small deletion on chromosome 17, removing the KANSL1 gene and other genes, or by a mutation in KANSL1. By analysing a large cohort of patients, we found that the degree of cognitive impairment is very […]
Neurogenetic evidence in the courtroom: a randomised controlled trial with German judges
Prominent court decisions and research suggest that presentation of neuro-genetic evidence may reduce the sentence of convicted psychopaths. In a mock case, we presented German judges with a hypothetical case vignette of aggravated battery and randomly assigned them to expert testimonies that either involved a neuro-genetic explanation of the offender’s psychopathy or not. We found […]
Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay
A homozygous mutation in the FTO gene encoding a 2-oxoglutarate dependent oxygenase was previously identified as the cause of a syndrome characterized by growth retardation and multiple malformations. No other pathogenic mutation in FTO has been identified as a cause of multiple congenital malformations. We investigated a 21-month-old girl who presented with growth retardation and […]
Melanoma Genetics
Although the majority of melanomas develop due to cell damage caused by ultraviolet (UV) radiation exposure, susceptibility to melanoma is also influenced by genetics. For some families, inheritance of particular melanoma ‘risk’ genes can predispose to developing melanoma. These are grouped into ‘high’, ‘medium’ and ‘low’ penetrance genes, where penetrance reflects the likelihood of melanoma […]
Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with Multiple Lentigines
Noonan syndrome with multiple lentigines, (NSML) formerly known as LEOPARD syndrome, has overlapping features with other RASopathies. Except for neurofibromatosis type 1, other disorders that result from dysregulated RAS/MAPK pathway are not known to be associated with neurogenic tumors. We identified four patients from three families with NSML, progressive neuropathy, enlarged nerves, massive burden of […]
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity
Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances, and distinctive brain MRI findings. Diagnosis and treatment of JS is challenging due to >28 associated genes and substantial clinical variability. This study provides a relatively unbiased view of the phenotypic range, genetic basis, and […]
Minichromosome maintenance complex component 8 (MCM8) gene mutations result in primary gonadal failure
Primary gonadal failure is characterized by a lack of spontaneous pubertal development, primary amenorrhea or early menopause in females, and underdeveloped testis and azoospermia in males. Its genetic causes remain mostly unknown. Variants of the minichromosome maintenance complex component 8 gene (MCM8) are significantly associated with early menopause. Mice lacking MCM8 are sterile. We sought […]
Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers
In March 2014 the International Gastric Cancer Linkage Consortium, a group of worldwide experts in the field of Hereditary Diffuse Gastric Cancer, held a consensus meeting in the Radboudumc in Nijmegen, The Netherlands. During this three-day meeting, the current evidence and world-wide experience for managing individuals with a family history of diffuse type gastric cancer […]
A founder MYBPC3 mutation results in HCM with a high risk of sudden death after the fourth decade of life
Hypertrophic Cardiomyopathy (HCM) is one of the most common inherited cardiac disorders with a prevalence of 1:500. It is characterized by unexplained left ventricular hypertrophy (from 13 mm to more than 35 mm) that develops in the absence of an underlying systemic condition or other cardiac disease. The most serious manifestations of HCM are sudden […]