Dentists, geneticists and clinician-researchers studying tooth defects are often confronted by patients with genetic disorders that have striking dental defects such as the absence of some or several teeth, loss or defects in tooth enamel, and cleft palate among others. These defects can have a significant impact on the health and quality of life of […]
Latest articles
MKS1 regulates ciliary INPP5E levels in Joubert syndrome (Contributed by Gisela Slaats)
Ciliopathies are disorders unified by shared pathophysiology and overlapping clinical phenotypes. MKS1 localizes to the base of the cilium, and MKS1 mutations are a major cause of the severe ciliopathy Meckel syndrome. We identified MKS1 mutations in nine families with the milder Joubert syndrome (JS), confirming a prior report linking MKS1 to JS. We demonstrate […]
High sensitivity sequencing reveals multi-organ somatic mosaicism causing DICER1 syndrome (Contributed by Dr. Leanne de Kock)
Somatic mosaicism arises following the occurrence of a mutation at some stage during the development of an embryo which is then propagated to only a select population of its cells. This phenomenon is being increasingly recognized as an important cause of isolated presentations of syndromes that are usually hereditary. The DICER1 syndrome is a rare […]
HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome (Contributed by Dr. David Bonthron)
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 […]
Zollino et al KANSL1 haploinsufficiency syndrome (Contributed by Prof. Marcella Zollino)
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 (Contributed by Dr. Johannes Fuss)
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 (Contributed by Dr. Hussein Daoud)
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 (Contributed by Dr. Jazlyn Read)
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 (Contributed by Drs. Dusica Babovic-Vuksanovic and Erin Conboy)
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 (Contributed by Dr. Dan Doherty)
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 […]