Genetic basis of endocrine pathology

T.V. Sorokman, P.M. Moldovan, N.O. Popeliuk, O.V. Makarova


The purpose of the review was analysis of literature data relating to the molecular genetic basis and diagnosis of endocrine pathology. We searched for published and unpublished researches using Pubmed as the search engine by the keywords: ‘genes’, ‘endocrine diseases’, ‘molecular diagnostics’, ‘prohormones’, ‘nuclear receptors and transcription factors’, taking into consideration studies conducted over the last 10 years, citation review of relevant primary and review articles, conference abstracts, personal files, and contact with expert informants. The criterion for the selection of articles for the study was based on their close relevance to the topic, thus out of 144 analyzed articles, the findings of the researchers covered in 32 articles were crucial. The described nosologies presented various heredi­tary forms of hypopituitarism, disturbances of steroid hormone biosynthesis, abnormal gender formation, monogenic forms of diabetes mellitus, endocrine tumors, etc. Pathology is identified that is associated with a mutation of genes encoding protein prohormones, receptors, steroid biosynthesis enzymes, intracellular signaling molecules, transport proteins, ion channels, and transcription factors. Among the endocrine diseases associated with defects in genes encoding protein prohormones, the defects of the GH1 gene are most common, the defects in the gene CYP21A2 (21-hydroxylase) are among diseases associated with defects in genes encoding enzymes. More often mutations of genes encoding proteins belong to the class of G-protein coupled receptors. Most of the mutations associated with MEN-2A are concentrated in the rich cysteine region of the Ret receptor. More than 70 monogenic syndromes are known, in which there is a marked tolerance to glucose and some form of diabetes mellitus is diagnosed, diabetes mellitus caused by mutation of the mitochondrial gene (mutation tRNALeu, UUR) is also detected. Of all the monogenic forms of obesity, the most common is obesity caused by mutation of melanocortin 4 receptor gene (MC4R). In patients with congenital hypothyroi­dism, the high frequency of HLA alleles (Bw44, Aw24, B18) and mutations in the genes TITF1, TITF2, FOXE1, PAX8 (transcription markers of normal thyroid ontogenesis of the thyroid gland) are described.


genes; endocrine diseases; molecular diagnostics; prohormones; nuclear receptors and transcription factors


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