Genomic medicine is still an emerging field. Scientists working at different institutions have developed naming systems and checklists and specialized databases that differ significantly from one to another; their utility is compromised by the many differences between them. The result is that sharing such data across the biomedical community has been difficult if not impossible. […]
Latest articles
Loss-of-function de novo mutations play an important role in severe human neural tube defects
Neural tube defects (NTDs) are very common and severe birth malformations that are caused by failure of neural tube closure. They are caused by a combination of genetic and environmental factors that remain largely unknown. Anencephaly and spina bifida are severe NTDs that affect reproductive fitness but are still prevalent across generations, suggesting a role […]
Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles Syndrome caused by a single FLNA mutation with combined gain-of-function and loss-of-function effects
Loss-of-function mutations of the FLNA gene cause X-linked periventricular nodular heterotopia (PNH) while gain-of-function mutations cause the Otopalatodigital (OPD) spectrum. These two conditions are known to be mutually exclusive phenotypes. We describe a family in which a woman and her three daughters exhibited a phenotype combining PNH, epilepsy and Melnick-Needles syndrome, a skeletal disorder assigned […]
A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B
Klippel-Feil anomaly (KFA) is a rare disorder encompassing fusion of the cervical spine, as well as low posterior hair line and limited neck mobility. Here we describe a mutation in a novel gene, MYO18B, which results in KFA along with muscular weakness. This is an association that has never been reported before. High resolution microscopy […]
Bilateral vestibular schwannomas in older patients: NF2 or chance?
We have previously estimated that one in two million people will develop bilateral vestibular schwannomas by chance. We show for the first time molecular proof that a man who developed bilateral vestibular schwannomas aged 52 and 67 years of age had developed these by independent events in the NF2 gene with no evidence of a […]
A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype
The recent discovery of a new mutation in the DNA mismatch repair gene PMS2 that is recurrent in the Inuit population surrounding Hudson Bay, Canada offers new insights suggesting that even a small, residual function of the gene in patients is sufficient to delay the age of onset of tumours. This new finding adds to […]
BRCA1 Circos: a visualisation resource for functional analysis of missense variants
Carriers of germline pathogenic variants in BRCA1 have a significantly increased risk of breast and ovarian cancers. However, genetic testing may also uncover a variant of unknown significance (VUS). Due to the rarity of these variants clinical and family data are usually lacking to determine cancer risk association. Functional assays can be used to assess […]
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing
Learning outcomes After completing this module you should be able to: Be aware of the genetic heterogeneity of ID and the diagnostic yield of different approaches to investigation Understand the challenges associated with interpreting variants identified by next generation sequencing (NGS) and the principles behind assigning causality Understand the strengths and weaknesses of a targeted […]
DCAF4, a novel gene associated with leucocyte telomere length
Leukocyte telomere length (LTL) is associated with a number of diseases. In particular, telomeres are short in patients with cardiovascular disease and long in patients with different types of cancer such as melanoma. In our study we identified a novel gene (DCAF4) associated with LTL in the general population. Our finding expands the spectrum of genes […]
MuSK – a novel gene for fetal death
Fetal akinesia deformation sequence (FADS) is a broad spectrum of syndromes characterized by reduced or loss of fetal movement, arthrogryposis, intrauterine growth restriction and developmental abnormalities. In this study, we identified a novel gene, MuSK (muscle-specific receptor tyrosine kinase), by whole exome sequencing in a Swedish family trio with fetuses affected by FADS. MuSK is […]