CAPN5mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular in...
...Published in Human Molecular Genetics
Becker muscular dystrophy severity is linked to the structure of dystrophin.
...Published in Human Molecular Genetics
In-frame exon deletions of the Duchenne muscular dystrophy (DMD) gene produce internally truncated proteins that typically lead to Becker muscular dystrophy (BMD), a milder allelic disorder of DMD. We hypothesized that differences in the structure of mutant dystrophin may be responsible for the clinical heterogeneity observed in Becker patients and...
Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known lo...
...Published in Human Molecular Genetics
Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and ...
Non-exomic and synonymous variants in ABCA4 are an important cause of Stargardt disease.
...Published in Human molecular genetics
Mutations in ABCA4 cause Stargardt disease and other blinding autosomal recessive retinal disorders. However, sequencing of the complete coding sequence in patients with clinical features of Stargardt disease sometimes fails to detect one or both mutations. For example, among 208 individuals with clear clinical evidence of ABCA4 disease ascertained...
Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis.
Published in Human molecular genetics
The Vesicle-associated membrane protein (VAMP)-Associated Protein B (VAPB) is the causative gene of amyotrophic lateral sclerosis 8 (ALS8) in humans. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective death of motor neurons leading to spasticity, muscle atrophy and paralysis. VAP proteins have ...
Exploring the genetic basis of chronic periodontitis: a genome-wide association study.
...Published in Human molecular genetics
Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (A...
Loss and gain of Drosophila TDP-43 impair synaptic efficacy and motor control leading to age-related neurodegeneration b...
...Published in Human molecular genetics
Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial and sporadic forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that either loss or gain of TDP-43 function, or both, cause disease formation. Here we have systematically compared loss- and gain-of-function of Drosophila TDP-43, TAR ...
Health and disease in 85 year olds: baseline findings from the Newcastle 85+ cohort study.
...Published in BMJ (Clinical research ed.)
This large cohort of 85 year olds showed good levels of both self rated health and functional ability despite significant levels of disease and impairment. Hypertension, ischaemic heart disease, atrial fibrillation, depression, and dementia may be underdiagnosed. Notable differences were found between the sexes: women outnumbered men and had more d...
Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney fu...
Published in Human Molecular Genetics
In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological kno...
Respiratory dysfunction by AFG3L2 deficiency causes decreased mitochondrial calcium uptake via organellar network fragme...
Published in Human molecular genetics
The mitochondrial protein AFG3L2 forms homo-oligomeric and hetero-oligomeric complexes with paraplegin in the inner mitochondrial membrane, named m-AAA proteases. These complexes are in charge of quality control of misfolded proteins and participate in the regulation of OPA1 proteolytic cleavage, required for mitochondrial fusion. Mutations in AFG3...
