problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl2017633174-178problendo-8604Research ArticleКлинические случаиCase ReportsГипопитуитаризм, обусловленный мутацией в гене PROP1, в сочетании с синдромом 47,XYY и частично открытым атриовентрикулярным каналом: обзор двух клинических случаевHypopituitarism due to mutation in the PROP1 gene in association with the 47,XYY karyotype and autosomal dominant atrioventricular septal defect: two case reportshttps://orcid.org/0000-0003-3922-2869ГубаеваДиляра НаилевнаGubaevaDilyara N.

ординатор

MD

gubaevadn@gmail.comhttps://orcid.org/0000-0001-6196-5322ОрловаЕлизавета МихайловнаOrlovaElizaveta M.

к.м.н., в.н.с.

PhD, leading researcher

elizaveta.orlova@mail.ruhttps://orcid.org/0000-0003-3396-8678ПанкратоваМария СтаниславовнаPankratovaMaria S.

к.м.н., в.н.с.

PhD, leading researcher

ms_pankratova@mail.ruhttps://orcid.org/0000-0003-3074-6930ВоронцовАлександр ВалерьевичVorontsovAlexander V.

д.м.н., проф.

PhD, MD, prof.

mrt@endocrincentr.ruhttps://orcid.org/0000-0003-1320-6561КареваМария АндреевнаKarevaMaria А.

к.м.н., в.н.с.

PhD, leading researcher

i_marusya@mail.ru<p>ФГБУ &laquo;Эндокринологический научный центр&raquo; Минздрава России</p>Россия<p>Endocrinology Research Centre</p>Russian Federation201715062017633174178Copyright &#x00A9; Губаева Д.Н., Орлова Е.М., Панкратова М.С., Воронцов А.В., Карева М.А., 20172017Губаева Д.Н., Орлова Е.М., Панкратова М.С., Воронцов А.В., Карева М.А.Gubaeva D.N., Orlova E.M., Pankratova M.S., Vorontsov A.V., Kareva M.А.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/8604

Использование методик генетического анализа дает возможность в клинической практике выявлять сочетание редких заболеваний у одного пациента. Рассматриваются два клинических случая гипопитуитаризма, обусловленного мутациями в гене PROP1. В первом случае гипопитуитаризм сочетается с синдромом 47,XYY, во втором — с частично открытым атриовентрикулярным каналом, наследуемым аутосомно-доминантным путем. Данные клинические наблюдения наглядно демонстрируют возможность наличия нескольких редких заболеваний у одного пациента. Морфология гипофиза при дефекте гена PROP1 имеет специфические особенности: инверсия сигнала на Т1- и Т2-взвешанных изображениях и изменение размеров гипофиза во времени. При наличии низкорослости, гормональных признаков вторичного гипопитуитаризма, сниженного уровня инсулиноподобного фактора-1 и характерных морфологических изменений гипофиза при магнитно-резонансной томографии рекомендуется целенаправленное проведение молекулярно-генетического анализа гена PROP1 без проведения пробы со стимуляцией секреции соматотропного гормона.

Application of genetic analysis in clinical practice enables identifying a combination of two rare diseases in one patient. We report two cases of patients with hypopituitarism due to PROP1 gene mutations in combination with the 47,XYY karyotype (case 1) and autosomal dominant partial atrioventricular septal defect (case 2). These clinical cases clearly demonstrate that several rare diseases can be present in one patient. The morphology of the pituitary gland has specific features in patients with a PROP1 gene mutation: signal inversion on T1- and T2-weighted images, as well as changes in size of the pituitary gland over time. In case of short stature, the hormonal evidence of secondary hypopituitarism, low IGF-1 levels, and specific morphological features observed in MRI images, we recommended carrying out molecular genetic analysis of the PROP1 gene without conducting growth hormone stimulation test.

гипопитуитаризмPROP1синдром 47XYYдефект атриовентрикулярной перегородкидефицит гормона ростаклинический случайhypopituitarismPROP147XYY syndromeatrioventricular septal defectgrowth hormone deficiencycase reportПрограмма «Альфа-Эндо»ReferencesRiepe FG, Partsch CJ, Blankenstein O, et al. Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation. J Clin Endocrinol Metab. 2001;86(9):4353-4357. doi: 10.1210/jcem.86.9.7828Riepe FG, Partsch CJ, Blankenstein O, et al. Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation. J Clin Endocrinol Metab. 2001;86(9):4353-4357. doi: 10.1210/jcem.86.9.7828Mody S, Brown MR, Parks JS. The spectrum of hypopituitarism caused by PROP1 mutations. Best Pract Res Clin Endocrinol Metab.2002;16(3):421-431. doi: 10.1053/beem.2002.0218Mody S, Brown MR, Parks JS. The spectrum of hypopituitarism caused by PROP1 mutations. Best Pract Res Clin Endocrinol Metab.2002;16(3):421-431. doi: 10.1053/beem.2002.0218Fluck C, Deladoey J, Rutishauser K, et al. Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg->Cys at codon 120 (R120C). J Clin Endocrinol Metab.1998;83(10):3727-3734. doi: 10.1210/jcem.83.10.5172Fluck C, Deladoey J, Rutishauser K, et al. Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg->Cys at codon 120 (R120C). J Clin Endocrinol Metab.1998;83(10):3727-3734. doi: 10.1210/jcem.83.10.5172Fluck C, Deladoey J, Rutishauser K, et al. Phenotypic variabi lity in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg->Cys at codon 120 (R120C). J Clin Endocrinol Metab. 1998;83(10):3727-3734. doi: 10.1210/jcem.83.10.5172Fluck C, Deladoey J, Rutishauser K, et al. Phenotypic variabi lity in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg->Cys at codon 120 (R120C). J Clin Endocrinol Metab. 1998;83(10):3727-3734. doi: 10.1210/jcem.83.10.5172Children and young adults with sex chromosome aneuploidy—follow-up, clinical and molecular studies. Minaki, Ontario, Canada, June 7-10, 1989. Birth Defects Orig Artic Ser. 1990;26(4):1-304.Children and young adults with sex chromosome aneuploidy—follow-up, clinical and molecular studies. Minaki, Ontario, Canada, June 7-10, 1989. Birth Defects Orig Artic Ser. 1990;26(4):1-304.Margari L, Lamanna AL, Craig F, et al. Autism spectrum disorders in XYY syndrome: two new cases and systematic review of the literature. Eur J Pediatr. 2014;173(3):277-283. doi: 10.1007/s00431-014-2267-9Margari L, Lamanna AL, Craig F, et al. Autism spectrum disorders in XYY syndrome: two new cases and systematic review of the literature. Eur J Pediatr. 2014;173(3):277-283. doi: 10.1007/s00431-014-2267-9Ferencz C, Loffredo CA, Correa-Villasenor A, Wilson PD. Atrioventricular septal defects with and without Down syndrome. In: Ferencz C, Loffredo CA, Correa-Villasenor A, Wilson PD. Genetic & Environmental Risk Factors of Major Cardiovascular Malformations: the Baltimore-Washington Infant Study 1981–1989. Armonk: Futura Publishing. 1997;103-122.Ferencz C, Loffredo CA, Correa-Villasenor A, Wilson PD. Atrioventricular septal defects with and without Down syndrome. In: Ferencz C, Loffredo CA, Correa-Villasenor A, Wilson PD. Genetic & Environmental Risk Factors of Major Cardiovascular Malformations: the Baltimore-Washington Infant Study 1981–1989. Armonk: Futura Publishing. 1997;103-122.Obermannova B, Pfaeffle R, Zygmunt-Gorska A, et al. Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects. Horm Res Paediatr. 2011;76(5):348-354. doi: 10.1159/000332693Obermannova B, Pfaeffle R, Zygmunt-Gorska A, et al. Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects. Horm Res Paediatr. 2011;76(5):348-354. doi: 10.1159/000332693Jacobs PA, Melville M, Ratcliffe S, et al. A cytogenetic survey of 11,680 newborn infants. Ann Hum Genet. 1974;37(4):359-376.Jacobs PA, Melville M, Ratcliffe S, et al. A cytogenetic survey of 11,680 newborn infants. Ann Hum Genet. 1974;37(4):359-376.Morel F, Roux C, Bresson JL. Sex Chromosome Aneuploidies in Sperm of 47,XYY Men. Arch Androl. 2009;43(1):27-36. doi: 10.1080/014850199262706Morel F, Roux C, Bresson JL. Sex Chromosome Aneuploidies in Sperm of 47,XYY Men. Arch Androl. 2009;43(1):27-36. doi: 10.1080/014850199262706El-Dahtory F, Elsheikha HM. Male infertility related to an aberrant karyotype, 47,XYY: four case reports. Cases J. 2009;2(1):28. doi: 10.1186/1757-1626-2-28El-Dahtory F, Elsheikha HM. Male infertility related to an aberrant karyotype, 47,XYY: four case reports. Cases J. 2009;2(1):28. doi: 10.1186/1757-1626-2-28Wong EC, Ferguson KA, Chow V, Ma S. Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY male. Hum Reprod. 2008;23(2):374-378. doi: 10.1093/humrep/dem377Wong EC, Ferguson KA, Chow V, Ma S. Sperm aneuploidy and meiotic sex chromosome configurations in an infertile XYY male. Hum Reprod. 2008;23(2):374-378. doi: 10.1093/humrep/dem377Moretti E, Anichini C, Sartini B, Collodel G. Sperm ultrastructure and meiotic segregation in an infertile 47, XYY man. Andrologia. 2007;39(6):229-234. doi: 10.1111/j.1439-0272.2007.00791.xMoretti E, Anichini C, Sartini B, Collodel G. Sperm ultrastructure and meiotic segregation in an infertile 47, XYY man. Andrologia. 2007;39(6):229-234. doi: 10.1111/j.1439-0272.2007.00791.xStochholm K, Juul S, Gravholt CH. Diagnosis and mortality in 47,XYY persons: a registry study. Orphanet J Rare Dis. 2010;5:15. doi: 10.1186/1750-1172-5-15Stochholm K, Juul S, Gravholt CH. Diagnosis and mortality in 47,XYY persons: a registry study. Orphanet J Rare Dis. 2010;5:15. doi: 10.1186/1750-1172-5-15Craig B. Atrioventricular septal defect: from fetus to adult. Heart. 2006;92(12):1879-1885. doi: 10.1136/hrt.2006.093344Craig B. Atrioventricular septal defect: from fetus to adult. Heart. 2006;92(12):1879-1885. doi: 10.1136/hrt.2006.093344Wilson L, Curtis A, Korenberg JR, et al. A large, dominant pedigree of atrioventricular septal defect (AVSD): exclusion from the Down syndrome critical region on chromosome 21. Am J Hum Genet. 1993;53(6):1262-1268.Wilson L, Curtis A, Korenberg JR, et al. A large, dominant pedigree of atrioventricular septal defect (AVSD): exclusion from the Down syndrome critical region on chromosome 21. Am J Hum Genet. 1993;53(6):1262-1268.Kumar A, Williams CA, Victorica BE. Familial atrioventricular septal defect: possible genetic mechanisms. Heart. 1994;71(1):79-81. doi: 10.1136/hrt.71.1.79Kumar A, Williams CA, Victorica BE. Familial atrioventricular septal defect: possible genetic mechanisms. Heart. 1994;71(1):79-81. doi: 10.1136/hrt.71.1.79

The authors declare that there are no conflicts of interest present.