Kaufman oculocerebrofacial syndrome (KOS) is a rare disorder affecting development and growth originally recognized 40 years ago. KOS is characterised by microcephaly, mental retardation, ocular anomalies, distinctive facial features, generalised hypotonia, and reduced growth. In this paper, exome sequencing was employed to identify UBE3B, encoding an E3 ubiquitin-protein ligase, as the gene mutated in KOS. […]
Latest articles
An X chromosome-wide association analysis identifies variants in GPR174 as a risk factor to Graves’ disease
Graves’ disease is an autoimmune illness mostly seen in female. The contribution of the X chromosomes to its risk has long been appreciated. We re-examined the X chromosome data from our recent study using a technology named genome-wide association study (GWAS). A single nucleotide polymorphism (SNP) which changes an amino acid within the G protein-coupled […]
Upregulation of RCAN1 causes Down syndrome-like immune dysfunction
People with Down syndrome (DS) (trisomy 21) have impaired immune function making them susceptible to infections and autoimmune disease. The molecular cause for this impairment is undetermined. Using mice we have found that an excess of RCAN1, a protein expressed at higher than normal levels in DS, adversely affects key immune functions, and that an […]
Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus
Intellectual disability (ID) is one of the most common disabilities worldwide, affecting nearly 2% of the global population. Here we examined patients from eight families suffering from a form of ID that is coupled with squint of the eye, and in each case found the same DNA mutation, in a gene called ADAT3. This gene […]
A novel syndrome of hypohidrosis and intellectual disability is linked to COG6 deficiency
Intellectual disability (ID) is a common disability in humans and comprises both isolated forms as well as forms that are associated with a constellation of other clinical problems i.e. syndromic ID. In this study, we describe an apparently novel syndromic ID in which patients have decreased sweating and brittle teeth. Using positional cloning techniques in […]
A new gene for childhood-onset pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) in children is a progressive and often fatal disease of the lung vessels, for which no curative therapy exists. PAH may be heritable: mutations in the BMPR2-gene have been found in about 15% of children with the disease. In a national cohort of Dutch children with unexplained PAH, we identified mutations […]
Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations
Nemaline myopathy (NM) is the most common non-dystrophic congenital myopathy and is most frequently caused by mutations in the nebulin gene. The sarcomeric protein nebulin plays a crucial role in skeletal muscle performance. NM patients with nebulin mutations have muscle weakness through mechanisms including a lower responsiveness to calcium. No therapy exists to treat muscle […]
Rhizomelic chondrodysplasia punctata and cardiac pathology
Rhizomelic Chondrodysplasia Punctata (RCDP) is a rare genetic disorder associated with symmetrical shortening of the upper arms and legs, contractures, cataracts and developmenatal delay. The levels of plasmalogens (major constituents of cellular membranes) are low. Although high levels of plasmalogens are normally found in the heart, heart abnormalities have not previously been strongly associated with […]
Meta-Analysis of Genome-Wide Studies Identifies MEF2C SNPs Associated with Bone Mineral Density at Forearm
This paper finds different variants in MEF2C are associated with forearm bone mineral density (BMD) compared to the MEF2C variants associated with femoral neck BMD. We conclude that these variants are likely independent signals that have different independent effects on the two BMD phenotypes. It is also possible that both associations arise from several rare […]
A new seipin-associated neurodegenerative syndrome
Seipin is a protein encoded by BSCL2 gene. BSCL2 mutations can produce congenital generalized lipodystrophy (Berardinelli-Seip syndrome). We have discovered that a novel BSCL2 mutation, c.985C>T, is responsible of a new severe degenerative brain disease, leading to death before age 9. This mutation causes an alternative splicing site leading to the skipping of BSCL2 exon […]