The mir-183 microRNA (miRNA) family is composed of mir-183, mir-96, and mir-182, which are coordinately expressed from a single genetic locus in vertebrates. This highly conserved miRNA family is essential for differentiation and function of the vertebrate inner ear. In 2009, 2 mutations in the human MIRN96 gene have been reported in 2 Spanish families affected by autosomal dominant nonsyndromic sensorineural hearing loss (AD-NSHL). This represented the first evidence implicating a point mutation within a miRNA in a Mendelian disease. We screened a total of 770 NSHL patients and 808 normal-hearing Italian controls for mutations in MIRN96, MIRN182, and MIRN183. Neither of the 2 previously reported MIRN96 mutations were found, suggesting that they might represent private mutations. Instead, at least one putative novel mutation within mir-96, +57T>C, was identified in a patient with a family history of AD-NSHL. The detected variant replaces a highly evolutionarily conserved nucleotide located outside the mature mir-96, and is predicted to reduce the stability of the pre-miRNA secondary structure (dG from -34.4 to -30.4 Kcal/Mol). Moreover, the variation occurs within the seed region of the mature mir-96*, which is processed from the complementary strand of the mir-96 precursor. The mir-96* seem to have been maintained throughout vertebrate evolution, although its sequence is only partially conserved. Very little is known about mir-96* expression and function. The effect of mir-96+57T>C on mir-96 processing as well as on mir-96* processing/target recognition is currently underway by ex-vivo expression experiments in human cell lines.
|Titolo:||Role of the microRNA-183 family in the pathogenesis of hereditary nonsyndromic hearing loss in the Italian population|
DUGA, STEFANO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
Settore BIO/11 - Biologia Molecolare
|Data di pubblicazione:||giu-2010|
|Enti collegati al convegno:||European Society of Human Genetics (ESHG)|
|Appare nelle tipologie:||01 - Articolo su periodico|