KCNJ11 encodes an important component of the potassium channel that plays a critical role in regulating the response of beta cells in the pancrease to changes in blood glucose level. Mutations in this gene can cause inappropriately reduced or elevated insulin secretion. In a large and extended consanguineous Saudi family, we show for the first […]
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Recurrent X chromosome-linked deletions: discovery of new genetic factors in male infertility
The etiology of altered spermatogenesis is unknown in about 40% of cases and a large proportion of it is likely related to still unknown genetic factors. The identification of the “missing” genetic causes is of importance both for genetic counseling and for the development of future etiologic therapies. Our study, by screening over 1200 subjects […]
Prenylation defects in inherited retinal diseases
To fulfil their specialised functions, retinal proteins are located at specific positions in photoreceptor cells. These cells consist of many different compartments. Proteins are transported between these compartments through their binding to other proteins or to membranous vesicles. To interact with other proteins or vesicles, proteins contain a hydrophobic lipid molecule, a prenyl group. Many […]
Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome
Using the largest patient cohort studied (1052 patients) with Rett syndrome (RTT), we investigated whether individual mutations give rise to the observed phenotypic variability. We identified groups of point mutations, deletions and insertions that were particularly severe in both typical and atypical RTT, as well as groups of mutations were less severe. Our data suggest […]
NECAP1 loss of function leads to a severe infantile epileptic encephalopathy
Epileptic encephalopathy (EE) describes a group of neurological disorders in which epilepsy is accompanied by an insult to the developing brain. Here we studied an extended family suffering from an early infantile form of EE, where the onset is within the first few months of life. We uncovered a mutation in a gene called NECAP1, […]
The novel mitochondrial 16S rRNA 2336T>C mutation is associated with hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a significant cause of sudden unexpected cardiac death in any age group. Here we reported a Chinese family with maternally transmitted HCM and atrioventricular block (AVB). DNA sequencing analysis identified a novel homoplasmic 2336T>C mutation, which disturbs the 2336U-A2438 base pair in the stem-loop structure of mitochondrial 16S rRNA domain III. […]
The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a beta cell phenotype
The authors have discovered that a specific mutation in the HNF4A gene causes Fanconi syndrome, where salt and protein loss by the kidneys leads to soft bones and short stature. People with this condition usually have to take tablets to replace the salts leaked by the kidneys, and the genes responsible haven’t been found until […]
Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia
As genetic testing of inherited diseases becomes ever more widely used, distinguishing between true disease-causing mutations and innocuous rare genetic variants is a critical issue in clinical genetics. Our new analysis method transfers known clinical mutations between evolutionarily related proteins, or paralogues, allowing us to identify mutations that affect parts of the protein intolerant to […]
Autism traits in the RASopathies
This ‘pathway’ approach investigates the Ras/MAPK signaling role in autism traits. A large sample representing genetic disorders (RASopathies) caused by mutations activating this pathway was compared with sibling controls and autism spectrum disorder (ASD) subjects. Each RASopathy (Neurofibromatosis type 1, Noonan syndrome, Costello syndrome, and cardio-facio-cutaneous syndrome) is associated with autism traits, with distinct distributions. […]
Direct-to-consumer pharmacogenomic testing is associated with increased physician utilisation
The impact of direct-to-consumer (DTC) pharmacogenomic testing on consumer behavior has not been previously studied. A large sample of adults purchased a DTC pharmacogenomic test and completed baseline and follow-up health behavior assessments. The pharmacogenomic test included testing for drug effectiveness or risk of side effects for 12 medications. At follow-up the 481 individuals who […]