Özet:
Identification of the genetic basis of a hereditary disease provides important information about the molecular mechanism of the disease and the function of the gene and could contribute to the development of therapeutic means. Linkage analysis is one of the most powerful methods used to map a disease gene locus. For a recessive disease, a consanguineous family is important for the identification of the disease locus since the affected individuals share the disease haplotype in the homozygous state, descending from a single ancestor. Whole exome sequencing is a very efficient method for the identification of the causative mutation. After the identification of the disease gene locus by linkage analysis, exome sequence analysis can be applied to find the causative mutation at the candidate locus. In this study, identification of the disease loci and the causative gene defects for six inherited disorders were attempted. The study families were afflicted with Congenital Disorder of Glycosylation (CDG), Myosin Storage Myopathy (MSM), Desmin Deficiency Myopathy (DDM), Hereditary Brain Tumors (HBT), Epilepsy, or Muscular Dystrophy (MD). Stopgain mutation SRD5A3 p.W19X was found in CDG family, missense mutation p.R1820W in MHY7 was identified in MSM family, and frameshift mutation p.N116Qfs*2 in DES in DDM family. Three mutations were identified in HBT family: frameshift p.E138Vfs*93 in CARHSP1, missense p.Y193C in RGS22 and p.E363G in METTL22. In Epilepsy family no disease locus could be identified. Synonymous mutation LMNA c.346C>T was identified in MD family.
