Published in The American Journal of Human Genetics
Nephronophthisis (NPH), an autosomal-recessive tubulointerstitial nephritis, is the most common cause of hereditary end-stage renal disease in the first three decades of life. Since most NPH gene products (NPHP) function at the primary cilium, NPH is classified as a ciliopathy. We identified mutations in a candidate gene in eight individuals from f...
Published in The American Journal of Human Genetics
Gillespie syndrome (GS) is a rare variant form of aniridia characterized by non-progressive cerebellar ataxia, intellectual disability, and iris hypoplasia. Unlike the more common dominant and sporadic forms of aniridia, there has been no significant association with PAX6 mutations in individuals with GS and the mode of inheritance of the disease h...
Published in The American Journal of Human Genetics
Computer simulations based on simplified representations are routinely used to explore the early steps of amyloid aggregation. However, when protein models with implicit solvent are employed, these simulations miss the effect of solvent induced correlations on the aggregation kinetics and lifetimes of metastable states. In this work, we apply the m...
Published in The American Journal of Human Genetics
The design of biomimetic complexes for the modeling of metallo-enzyme active sites is a fruitful strategy for obtaining fundamental information and a better understanding of the molecular mechanisms at work in Nature's chemistry. The classical strategy for modeling metallo-sites relies on the synthesis of metal complexes with polydentate ligands th...
Published in American journal of human genetics
Rare-variant association studies in common, complex diseases are customarily conducted under an additive risk model in both single-variant and burden testing. Here, we describe a method to improve detection of rare recessive variants in complex diseases termed RAFT (recessive-allele-frequency-based test). We found that RAFT outperforms existing app...
Published in Apidologie
Pantoea agglomerans is a possible biocontrol agent against fire blight (Erwinia amylovora) and a facultative pathogen of humans. Isolates were gathered from flowers, pollen loads, honey sacs, and freshly stored nectar (FSN). Under artificial inoculation conditions, strains completely lost their culturability at 24 °C after 120 h of incubation in ho...
Published in American journal of human genetics
Cytochrome c oxidase (COX) deficiency is a frequent biochemical abnormality in mitochondrial disorders, but a large fraction of cases remains genetically undetermined. Whole-exome sequencing led to the identification of APOPT1 mutations in two Italian sisters and in a third Turkish individual presenting severe COX deficiency. All three subjects pre...
Published in American journal of human genetics
Intragenic copy-number variants (CNVs) contribute to the allelic spectrum of both Mendelian and complex disorders. Although pathogenic deletions and duplications in SPAST (mutations in which cause autosomal-dominant spastic paraplegia 4 [SPG4]) have been described, their origins and molecular consequences remain obscure. We mapped breakpoint juncti...
Published in American journal of human genetics
Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly...
Published in The American Journal of Human Genetics
Ciliopathies are a group of hereditary disorders associated with defects in cilia structure and function. The distal appendages (DAPs) of centrioles are involved in the docking and anchoring of the mother centriole to the cellular membrane during ciliogenesis. The molecular composition of DAPs was recently elucidated and mutations in two genes enco...
