Non-progressive cerebellar hypoplasias are rare developmental disorders leading to movement incoordination and intellectual disability. In an affected eight year-old girl, we identified an exchange between chromosomes X and 8 (translocation X;8). The Protein Tyrosine Kinase 2 (PTK2) and THO complex 2 (THOC2) gene structure was altered and both proteins were reduced to at least half […]
Latest articles
Identification of well-differentiated gene expressions between Han Chinese and Japanese using genome-wide microarray data analysis
Comparing and identifying phenotypic differences between genetically close-related populations is interesting but challenging. Here we attempt to understand the difference between Han Chinese and Japanese via the analysis of gene expression data which we assume to be a proxy measure of phenotypic differences. We first identified expression showing significant differences between the two populations (about […]
CDH1 Germline Mutations and the Hereditary Diffuse Gastric and Lobular Breast Cancer Syndrome: a Multicentre Study
Mutations in CDH1 cause the Hereditary Diffuse Gastric Cancer Syndrome. We report the largest series to date of index cases with a germline CDH1 mutation, and propose a revision of the testing criteria as a substantial proportion of our cases did not fulfil them. More specifically, we show that patients with a personal or family […]
Refining the role of pms2 in Lynch syndrome: germline mutational analysis improved by comprehensive assessment of variants
Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is caused by germline mutations in mismatch repair genes. Borràs and collaborators assessed the pathogenicity of variants of unknown significance detected in the mutational analysis of PMS2 gene using a comprehensive strategy. Pathogenic PMS2 mutations were detected in 9 of 13 (69%) candidate patients: seven […]
Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly
Mutations in TSC1 or TSC2 cause Tuberous Sclerosis Complex (TSC) a multisystemic disorder with many features including intellectual disability (ID). TSC1, TSC2 and TBC1D7 form a complex that inhibits mTORC1 signaling and limits cell growth. Using homozygosity mapping and exome sequencing to study a consanguineous family with ID and megalencephaly, we identified, in the affected individuals, […]
Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome
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. […]
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 […]