Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies

• DOI: 10.1038/srep26440
• Publication Date: 2016-05-24T17:17:56Z
• Authors: T. V. Andreeva; T. V. Tyazhelova; V. N. Rykalina; F. E. Gusev; A. Yu. Goltsov; O. I. Zolotareva; M. P. Aliseichik; T. A. Borodina; A. P. Grigorenko; D. A. Reshetov; E. K. Ginter; S. S. Amelina; R. A. Zinchenko; E. I. Rogaev
• Keywords: Male; Models, Molecular; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie; 0301 basic medicine; 570; Mutation, Missense; 610; Anoctamins; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit; Article; Muscular Dystrophies; Russia; Molecular Genetics; 03 medical and health sciences; Genetics research; Exome Sequencing; Genetics; Humans; Musculoskeletal Diseases; Child; Genetic Association Studies; Cementoma; Disease genetics; Medical genetics; Computational Biology; Sequence Analysis, DNA; Osteogenesis Imperfecta; Jaw Neoplasms; Pedigree; Next-generation sequencing; Female

Abstract 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 Russian origin, history dental tumors jaws, in correspondence to original clinical diagnosis cementoma consistent gigantiform (GC, OMIM: 137575). Whole exome sequencing revealed heterozygous missense mutation c.1067G > A (p.Cys356Tyr) ANO5 gene these patients. To date, autosomal-dominant mutations have been described for gnathodiaphyseal dysplasia (GDD, 166260) multiple recessive muscle dystrophies (OMIM: 613319, 611307); same amino acid (Cys) at position 356 is mutated GDD. These genetic data similar phenotypes demonstrate that GC GDD likely type pathology. Our illustrate significance single amino-acid particular tissue Modifying role variations another on severity monogenic trait pathology also suggested. Finally, propose model explaining tissue-specific manifestation clinically distant diseases linked one gene.