Genetic basis of endocrine pathology

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

Abstract


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 We searched for published and unpublished researches using Pubmed as the search engine by the keywords: ‘genes’, ‘endocrine diseases’, ‘molecular diagnostics’, ‘prohormones’, ‘nuclear receptors and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.

Keywords


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

References


Tyulpakov AN. The role of molecular genetics in the diagnosis and treatment of endocrine diseases. A brief description of the monogenic forms of hereditary endocrinopathies diagnosed in Endocrinological Research Center FGU ENC during the 15-year period (1996-2010). Problemi Endokrinologіji. 2011;1:26-34. (In Russian). doi: 10.14341/probl201157126-34.

Giordano M. Genetic causes of isolated and combined pituitary hormone deficiency. Best Pract Res Clin Endocrinol Metab. 2016 Dec;30(6):679-91. doi: 1016/j.beem.2016.09.005.

Rostomyan L, Beckers A. Screening for genetic causes of growth hormone hypersecretion. Growth Horm IGF Res. 2016 Oct-Dec;30-31:52-7. doi: 10.1016/j.ghir.2016.10.004.

Aslan IR, Ranadive SA, Valle I, et al. The melanocortin system and insulin resistance in humans: insights from a patient with complete POMC deficiency and type 1 diabetes mellitus. J Obes (Lond). 2014 Jan;38(1):148-51. doi: 10.1038/ijo.2013.53.

Tyulpakov AN, Kalynchenko NYu. Clinical and molecular-genetic characteristics of 10 cases with congenital adrenal hypoplasia caused by DAX1 gene defects. Problemi Endokrinologіji. 2010;2:3-9. (In Russian). doi: 10.14341/probl20105623-9.

Dzeranova LK, Tyul'pakov AN, Pyharova EA, et al. A new mutation in CYP17 gene: a description of the clinical case. Problemi Endokrinologіji. 2006;6:41-4. (In Russian).

Amiraslanova MM, Mamedova NF, Sosnova EA. The role of 21-hydroxylase deficiency in the genesis of congenital adrenal hyperplasia. Nauchnye vedomosty Belgorodskogo gosudarstvennogo universyteta. Seriya: Meditsina. Farmatsiya. 2011;10(105):44-7. (In Russian).

Zelynskaya NB, Pohadaeva NL, Hloba EV, Shevchenko YYu, Behutova TN, Khoroshaya OA, Malashonok VB. The state of the hormonal status of children with congenital adrenocortical dysfunction due to deficiency of 21-hydroxylase. Perinatologiya i pediatriya. 2015;1(61):54-9. (In Russian). doi: 10.15574/PP.2015.61.54.

Shozu M, Fukami M, Ogata T. Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis. Expert Rev Endocrinol Metab. 2014;9(4):397-409. doi: 10.1586/17446651.2014.926810.

Kalinchenko NYu, Zubkova NA, Tyulpakov AN. Clinical description and molecular-genetic verification of 2 cases of isolated mineralocorticoid insufficiency due to a deficiency of aldosterone synthase. Problemi Endokrinologіji. 2009;1:28-31. (In Russian).

Foster SR, Roura E, Molenaar P, Thomas WG .G protein-coupled receptors in cardiac biology: old and new receptor. Biophys Rev. 2015 Mar;7(1):77-89. doi: 10.1007/s12551-014-0154-2.

Michigami T. Disorders Caused by Mutations in Calcium-Sensing Receptor and Related Diseases. Clin Calcium. 2017;27(4):521-7. (In Japanese). doi: CliCa1704521527.

Duan K, Gomez Hernandez K, Mete O. Clinicopathological correlates of hyperparathyroidism. J Clin Pathol. 2015;68(10):771-87. doi: 10.1136/jclinpath-2015-203186.

Vitebskaya AV, Petryaikina EE, Razumovsky AYu, et al. A case of severe neonatal hyperparathyroidism due to defect in calcium receptor. Problemi Endokrinologіji. 2010;4:27-33. (In Russian). doi: org/10.14341/probl201056427-33.

Hannan FM, Nesbit MA, Zhang C, et al. Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Molec Genet. 2012:21:2768-78 PubMed: 22422767. doi: 10.1093/hmg/dds105.

Inden M, Iriyama M, Zennami M. The type III transporters (PiT-1 and PiT-2) are the major sodium-dependent phosphate transporters in the mice and human brains. Brain Res. 2016;15,1637:128-36. doi: 10.1016/j.brainres.2016.02.032.

Laryna AA, Troshyna EA, Yvanova ON. Autoimmune polyglandular syndromes in the adults: genetic and immunological diagnostic criteria. Problemi Endokrinologіji. 2014;60(3):43-52. (In Russian). doi: 10.14341/probl201460343-52.

Turton JP, Reynaud R, Mehta A, et al. Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency. J Clin Endocrinol Metab. 2005;90:8:4762-70. doi: 10.1210/jc.2005-0570.

Kolodkina AA, Karmanov ME, Kalinchenko NYu, et al. The clinical, hormonal and molecular genetic characteristics of three cases of impaired sex formation (NFP) 46XY, caused by a deficiency of 5-reductase type II. Problemi Endokrinologіji. 2010;3:34-40. (In Russian). doi: 10.14341/probl201056334-40.

Bonomi M, Libri DV, Guizzardi F, et al. ‘New understandings’ of the genetic basis of isolated idiopathic central hypogonadism. Asian Journal of Andrology. 2012;14(1):49-56. doi: 10.1038/aja.2011.68.

Kuraeva TL, Zylberman LY, Tytovich EV, Peterkova VA. Genetics of monogenic forms of diabetes mellitus. Saharnyj diabet. 2011;1:20-7. (In Russian). doi: 10.14341/2072-0351-6246.

Zelinska NB, Globa YeV, Pogadaeva NL. Statistics of diabetes in children in Ukraine. Klinichna endokrynolohiya ta endokrynna khirurhiya. 2013;1(42):80-3. (In Ukrainian).

Dedov YY, Zubkova NA, Arbatskaya NYu, et al. MODY type 2: clinical and molecular-genetic characteristics of 13 cases of the disease. The first description of MODY in Russia. Problemi Endokrinologіji. 2003;3:3-7. (In Russian). doi: 10.14341/probl20095533-7.

Ellard S, Ellard S, Lango H Allen, De Franco E, et al. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia. 2013;56(9):1958-63.  doi: 10.1007/s00125-013-2962-5.

Global IDF/ISPAD Guideline for diabetes in childhood and adolescence. Pediatr Diabetes. 2009;10(12):1-210.

Globa YeV. Neonatal diabetes in Ukraine: modern diagnostic and therapeutic approaches. Klinichna endokrynologiya ta endokrynna khirurgiya. 2015;2(50):71-5. (In Ukrainian).

Alghamdi AB, Alsaedi KA, Aljasser A, Altawil A, Naglaa M Kamal. Extended clinical features associated with novel Glis3 mutation: a case report. BMC Endocrine Disorders. 2017;17:14. doi: 10.1186/s12902-017-0160-z.

Farooqi S, O’Rahilly S. Genetics of obesity in humans. Endocr Rev. 2006;27(7):710-18. doi: 10.1210/er.2006-0040.

Heianza Y, Qi L. Gene-Diet Interaction and Precision Nutrition in Obesity. Int J Mol Sci. 2017 Apr 7;18(4):E787. doi: 10.3390/ijms18040787.

Peterkova VA, Vasyukova OV, Tyul'pakov AN. Non-immune thyrotoxicosis caused by an activating mutation of the thyrotropic hormone receptor gene (the first description in Russia). Problemi endokrynologiji. 2009;2:48-50. (In Russian). doi: 10.14341/probl200955248-50.

Hannoush ZC, Weiss RE. Defects of Thyroid Hormone Synthesis and Action. Еndocrinol Metab Clin North Am. 2017;46(2):375-88. doi: 10.1016/j.ecl.2017.01.005.

Wang F, Liu C, Jia X, et al. Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis. Clin Chim Acta. 2017;25(470):36-41. doi: 10.1016/j.cca.2017.04.020.




DOI: https://doi.org/10.22141/2224-0721.13.4.2017.106650

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

 

© "Publishing House "Zaslavsky", 1997-2017

 

 Яндекс.МетрикаSeo анализ сайта Рейтинг@Mail.ru