DEOGEN2: prediction and interactive visualization of single amino acid variant deleteriousness in human proteins.

High-throughput sequencing methods are generating enormous amounts of genomic data, giving unprecedented insights into human genetic variation and its relation to disease. An individual human genome contains millions of Single Nucleotide Variants: to discriminate the deleterious from the benign ones, a variety of methods have been developed that predict whether a protein-coding variant likely affects the carrier individual's health. We present such a method, DEOGEN2, which incorporates heterogeneous information about the molecular effects of the variants, the domains involved, the relevance of the gene and the interactions in which it participates.

Bi-allelic variants in encoding the ligand to GPR56 are associated with cobblestone-like cortical malformation, white matter changes and cerebellar cysts.

Background: Collagens are one of the major constituents of the pial membrane, which plays a crucial role in neuronal migration and cortical lamination during brain development. Type III procollagen, the chains of which are encoded by , is the ligand of the G protein-coupled receptor 56 (GPR56), also known as adhesion G protein-coupled receptor G1. Bi-allelic mutations in give rise to cobblestone-like malformation, white matter changes and cerebellar dysplasia.

Convert your favorite protein modeling program into a mutation predictor: "MODICT".

Background: Predict whether a mutation is deleterious based on the custom 3D model of a protein.

Results: We have developed MODICT, a mutation prediction tool which is based on per residue RMSD (root mean square deviation) values of superimposed 3D protein models. Our mathematical algorithm was tested for 42 described mutations in multiple genes including renin (REN), beta-tubulin (TUBB2B), biotinidase (BTD), sphingomyelin phosphodiesterase-1 (SMPD1), phenylalanine hydroxylase (PAH) and medium chain Acyl-Coa dehydrogenase (ACADM).

I-PV: a CIRCOS module for interactive protein sequence visualization.

Summary: Today's genome browsers and protein databanks supply vast amounts of information about proteins. The challenge is to concisely bring together this information in an interactive and easy to generate format.

Availability And Implementation: We have developed an interactive CIRCOS module called i-PV to visualize user supplied protein sequence, conservation and SNV data in a live presentable format.

Thin genu of the corpus callosum points to mutation in FOXG1 in a child with acquired microcephaly, trigonocephaly, and intellectual developmental disorder: a case report and review of literature.

The FOXG1 syndrome is emerging as a relative new entity in paediatric neurology. We report a boy with acquired microcephaly, mental retardation and a thin genu of the corpus callosum. The combination of these findings led to mutation analysis of FOXG1.

Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: case study and literature review.

Background: The BIG2 protein, coded by ARFGEF2 indirectly assists neuronal proliferation and migration during cortical development. Mutations in ARFGEF2 have been reported as a rare cause of periventricular heterotopia.

Methods: The presence of periventricular heterotopia, acquired microcephaly and suspected recessive inheritance led to mutation analysis of ARFGEF2 in two affected siblings and their healthy consanguineous parents, after mutations in FLNA had been ruled out.