(C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Alternative pre-mRNA splicing plays a key role in the control of gene expression in both neurons and glial cells, and failure or dysregulation of these splicing events can cause FK866 ic50 developmental abnormalities and lead to the development of pathology.
Schizophrenia is a common mental disorder that presents as a complex condition. Many factors, of genetic, epigenetic and environmental etiology, such as developmental abnormalities in myelination, synapses and neurotransmission, have been implicated in this disorder. Intriguingly, aberrant alternative splicing of genes related to neurodevelopment and neural function has been detected in schizophrenia and related disorders. In this review, we discuss the aberrant splicing of specific genes for each candidate cause of schizophrenia. Finally, we discuss the only example that has been researched in detail, from the cause to clarification of the mechanism, in ongoing studies into the associations between brain disorders and abnormal splicing. (C) 2010 Elsevier
Ltd. All rights reserved.”
“Introduction: Collagen type IV related nephropathies are due to the defects in collagen IV genes COL4A3, COL4A4, or COL4A5 and comprise a spectrum of phenotypes ranging from Alport Syndrome (AS) to its mild variants, termed as familial haematuria or thin basement membrane nephropathy. Classical AS is a progressive renal disease presenting with a triad of progressive hematuric nephritis and typical extra-renal Ilomastat complications, such
as sensorineural hearing loss (SNHL) and variable ocular anomalies. The mode of inheritance in AS is X-linked in 85%, autosomal recessive in 15%, and autosomal dominant in rare cases.\n\nObjectives: This study aims to identify underlying mutation in multiple individuals from a large consanguineous Saudi family with inherited nephropathy, Ispinesib chemical structure including our index patient who manifested all the features of classical AS.\n\nPatients and methods: Patients were diagnosed by nephrologists and clinical geneticists. All the individuals underwent clinical, audiological and ophthalmological evaluation. Blood samples were collected after written informed consent. DNA extraction, homozygosity mapping and PCR amplification followed standard methodologies.\n\nResults: The disease locus was mapped to 2q36.3, where both COL4A3 and COL4A4 reside. Sanger sequencing of COL4A3 and COL4A4 revealed an underlying novel homozygous disease-causing COL4A4 mutation (c.2420delG; p.G807fsX60) in the affected proband. Considerable phenotypic variability segregating with this COL4A4 mutation in our study family is documented. The homozygous mutants were manifesting end-stage renal disease (FSRD) in their adolescence, while the heterozygous carrier members were presenting with considerable phenotypic heterogeneity ranging from intermittent hematuria to late onset ESRD.