Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G > A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene.
Background: Polymorphisms and disruption of the expression profile of miRNA genes are associated with systemic diseases (autoimmune and cardiovascular diseases). The aim of the study: To study the localization of miRNA binding sites to mRNA in cis-regulatory regions of genes and in the coding sequences of DNA (CDS) associated in our studies with early and late atherosclerosis, and to search for possible localization of binding sites to microRNAs with gene sites (PPARGC1A; LIPC; PON1; APOE; LPL; APOC3; EDN; TNFα; SERPINE1). Materials and methods: The search for homologous micro RNA motifs was carried out in the cisregulatory regions of the studied genes with the help of the bio-information package MEME Suite. Known miRNAs were taken from the miRBase database (http://mirbase.org/). Nucleotide sequences of cis-regulatory regions and gene introns were obtained from the NCBI database (http://www.ncbi.nlm.nih.gov/) using a set of scripts, IFITCH, designed to automatically retrieve data from NCBI sequences. The "miRBase" database was analyzed using automated search for binding sites in the original sequence using the MScanner classifier. 28645 microRNAs were registered (http://www.mirbase.org). Results: The results of the bioinformational search for the localization of motifs homologous to known microRNAs before and after the gene, as well as in the coding protein sequences and introns of the following genes: PON1, APOC3, LIPC, LPL, APOE, PPARGC1A, TNF, EDN, SERPIN showed that in genes and intergenic spaces there are a large number of motifs homologous to mature micro-RNA. The greatest absolute number of motifs is localized within the PPARGC1A gene-22 microRNAs. However, if we consider the relative frequency
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