Previous studies have convincingly shown that genetic variants in the genes HFE and TMPRSS6 are associated with the iron parameters serum iron, ferritin, transferrin saturation and total iron binding capacity. It was commonly thought that these associations could be explained by the intermediate effect of the genes on serum hepcidin, the central regulatory molecule of […]
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Digenic inheritance in medical genetics
Digenic inheritance (DI) of a disease in a family means that the variants at two genes or loci explain which individuals are affected or unaffected more clearly than the genotypes at one locus alone. This article catalogs case studies of human DI, since the first such example was published in 1994. One objective is to […]
Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy
Paclitaxel is a microtubule-binding drug widely used to treat several solid tumors. The paclitaxel dose-limiting toxicity is peripheral neuropathy, which is dose-cumulative and occurs in about one third of the patients. It exhibits a large interindividual variability of unknown molecular basis. We have conducted a GWAS in patients uniformly treated with paclitaxel/carboplatin by which we […]
Meta-Analysis of Genome-Wide Studies Identifies MEF2C SNPs Associated with Bone Mineral Density at Forearm
This paper finds very 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 […]
Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy with facial dysmorphism
Infantile neuroaxonal dystrophy (INAD) is a recessive disease that results in total neurologic degeneration and death in childhood. A family with two INAD sibs without mutation in PLA2G6, the known gene for INAD, was investigated. NALCN was identified as the gene responsible for the disease. The gene protein forms an ion channel that has a […]
A de novo X;8 translocation creates a PTK2-THOC2 gene fusion with THOC2 expression knockdown in a patient with psychomotor retardation and congenital cerebellar hypoplasia
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 […]
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, […]