Vestnik dermatologii i venerologiiVestnik dermatologii i venerologiiВестник дерматологии и венерологии0042-46092313-6294Rossijskoe Obschestvo Dermatovenerologov i Kosmetologov3210.25208/0042-4609-2014-90-3-53-59SHORT COMMUNICATIONКРАТКИЕ СООБЩЕНИЯRevisited diagnostics of hereditary epidermolysis bullosaК вопросу о диагностике врожденного буллезного эпидермолизаAlbanovaV. I.АльбановаВ. И.
Russian Federation
ChikinV. V.ЧикинВ. В.
Russian Federation
EpishevR. V.ЕпишевР. В.
Russian Federation
epishev@cnikvi.ruState Research Center of Dermatovenereology and Cosmetology, Ministry of healthcare of the Russian FederationФГБУ «Государственный научный центр дерматовенерологии и косметологии» Минздрава России24062014903535924082017Copyright ©; 2014, Albanova V.I., Chikin V.V., Epishev R.V.Copyright ©; 2014, Альбанова В.И., Чикин В.В., Епишев Р.В.2014Albanova V.I., Chikin V.V., Epishev R.V.Альбанова В.И., Чикин В.В., Епишев Р.В.https://creativecommons.org/licenses/by/4.0https://vestnikdv.ru/jour/article/view/32

Hereditary epidermolysis bullosa is a big group of hereditary diseases with the main manifestations in the form of blisters on the skin and mucous coat after slight mechanical injuries. It is not always possible to diagnose this disease based on the clinical picture. The article discusses current laboratory diagnostics methods for hereditary epidermolysis bullosa including immunofluorescence antigen mapping (IFM), transmission electron microscopy (TEM) and genetic analysis (molecular or DNA diagnostics) as well as their advantages and disadvantages. TEM determines the micro splitting level and nature of ultrafine changes in the area of the dermoepidermal junction; at the same time, such tests need special expensive equipment. Substantial experience is also needed to analyze the resulting submicroscopic images. IFM determines whether expression of the affected protein related to the disease development is reduced or absent; however, invalid (false positive or false negative) results can be obtained in patients with the reduced expression of the affected protein. Genetic analysis plays a key role for prenatal diagnostics. Therefore, to make an exact diagnosis of hereditary epidermolysis bullosa, it is expedient to apply IFM, TEM and genetic analysis. The need to set an exact diagnosis of the disease is related to the fact that the promising treatment methods being currently developed are aimed at treating patients with certain forms of the disease.

Врожденный буллезный эпидермолиз - большая группа наследственных заболеваний, основным проявлением которых является образование пузырей на коже и слизистых оболочках после незначительной механической травмы. Клиническая картина не всегда позволяет установить точный диагноз болезни. Рассмотрены современные методы лабораторной диагностики врожденного буллезного эпидермолиза - иммунофлюоресцентное антигенное картирование (ИАК), трансмиссионная электронная микроскопия (ТЭМ) и генетический анализ (молекулярная или ДНК-диагностика), их достоинства и недостатки. ТЭМ позволяет определять уровень микрорасщепления и характер ультратонких изменений в зоне дермоэпидермального соединения, однако для проведения исследований требуется дорогостоящее специальное оборудование. Для анализа полученных электронно-микроскопических изображений необходим большой опыт. ИАК позволяет выявить снижение или отсутствие экспрессии белка, с дефектом которого связано развитие болезни, однако возможны ошибочные (ложноположительные или ложноотрицательные) результаты у пациентов со сниженной экспрессией дефектного белка. Генетический анализ играет ключевую роль в пренатальной диагностике. Таким образом, для установления точного диагноза врожденного буллезного эпидермолиза целесообразно использование ИАК, ТЭМ и генетического анализа. Необходимость точной диагностики заболевания связана с тем, что разрабатываемые в настоящее время перспективные методы терапии направлены на лечение больных с определенными формами болезни.

врожденный буллезный эпидермолизтрансмиссионная электронная микроскопияиммунофлюоресцентное антигенное картированиемолекулярная диагностикапренатальная диагностикагенетическое консультированиеhereditary epidermolysis bullosatransmission electron microscopyimmunofluorescence antigen mappingmolecular diagnosticsprenatal diagnosticsgenetic consultingFine J.-D. Inherited epidermolysis bullosa. Orphanet J Rare Dis 2010; 5: 12.Fine J.-D., Eady R.A., Bauer E.A. et al. The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol 2008; 58 (6): 931-950.Anton-Lamprecht I., Schnyder U.W. Epidermolysis bullosa herpetiformis Dowling-Meara: a report of a case and pathomorphogenesis. Dermatologica 1982; 164: 221-235.Eady R.A., Dopping-Hepenstal P.J. Transmission electron microscopy for the diagnosis of epidermolysis bullosa. Dermatol Clin 2010; 28: 211-222.Pohla-Gubo G, Cepeda-Valdes R, Hintner H. Immunofluorescence mapping for the diagnosis of epidermolysis bullosa. Dermatol Clin 2010; 28: 201-210.Cepeda-Valdés R, Pohla-Gubo G, Borbolla-Escoboza JR et al. Immunofluorescence mapping for diagnosis of congenital epidermolysis bullosa Actas Dermosifiliogr. 2010; 101(8): 673-682.Intong L.R., Murrell D.F. How to take skin biopsies for epidermolysis bullosa. Dermatol Clin 2010; 28: 197-200.Solovan C., Ciolan M., Olariu L. The biomolecular and ultrastructural basis of epidermolysis bullosa. Acta Dermatovenerol Alp Panonica Adriat 2005; 14: 127-135.Yiasemides E., Walton J., Marr P. et al. A comparative study between transmission electron microscopy and immunofluorescence mapping in the diagnosis of epidermolysis bullosa. Am J Dermatopathol 2006; 28: 387-394.Castiglia D., Zambruno G. Molecular testing in epidermolysis bullosa. Dermatol Clin 2010; 28: 223-229.Varki R., Sadowski S., Pfender E., Uitto J. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. J Med Genet 2006; 43: 641-652.Varki R., Sadowski S., Uitto J., Pfender E. Epidermolysis bullosa. II. Type vIi collagen mutations and phenotype-genotype correlations in the dystrophic subtypes. J Med Genet 2007; 44: 181-192.van den Akker P.C., van Essen A.J., Kraak M.M. et al. Long-term follow-up of patients with recessive dystrophic epidermolysis bullosa in the Netherlands: expansion of the mutation database and unusual phenotype-genotype correlations. J Dermatol Sci 2009; 56: 9-18.Nischler E., Klausegger A., Hüttner C. et al. Diagnostic pitfalls in newborns and babies with blisters and erosions. Dermatol Res Pract 2009; 2009: 320403.Rodeck C.H., Eady R.A., Gosden C.M. Prenatal diagnosis of epidermolysis bullosa letalis. Lancet 1980; 1: 949-952.Fassihi H., McGrath J.A. Prenatal diagnosis of epidermolysis bullosa. Dermatol Clin 2010; 28 (2): 231-237.Pasmooij A.M., Pas H.H., Bolling M.C., Jonkman M.F. Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3. J Clin Invest 2007; 117 (5): 1240-1248.Pasmooij A.M., Pas H.H., Deviaene F.C. et al. Multiple correcting COL17A1 mutations in patients with revertant mosaicism of epidermolysis bullosa. Am J Hum Genet 2005; 77 (5): 727-740.Alfirevic Z., Sundberg K., Brigham S. Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Database Syst Rev 2003; (3): CD003252.Renwick P., Ogilvie C.M. Preimplantation genetic diagnosis for monogenic diseases: overview and emerging issues. Expert Rev Mol Diagn 2007; 7: 33-43.Svetlakov A.V., Markova E.V., Kazantseva O.M. et al. Voprosy mediko-geneticheskogo konsul'tirovaniya pri preimplantatsionnoy geneticheskoy diagnostike. Medical Genetics 2008; 7 (12): 16-24.Devroey P., Van Steirteghem A. A review of ten years experience of ICSI. Hum Reprod Update 2004; 10: 19-28.Handyside A.H., Kontogianni E.H., Hardy K. et al. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990; 344: 768-770.Cserhalmi-Friedman P.B., Tang Y., Adler A. et al. Preimplantation genetic diagnosis in two families at risk for recurrence of Herlitz junctional epidermolysis bullosa. Exp Dermatol 2000; 9: 290-297.Fassihi H., Grace J., Lashwood A. et al. Preimplantation genetic diagnosis of skin fragility-ectodermal dysplasia syndrome. Br J Dermatol 2006; 154: 546-550.Thornhill A.R., Pickering S.J., Whittock N.V. et al. Preimplantation genetic diagnosis of compound heterozygous mutations leading to ablation of plakophilin-1 (PKP1) and resulting in skin fragility ectodermal dysplasia syndrome: a case report. Prenat Diagn 2000; 20: 1055-1062.Renwick P., Trussler J., Lashwood A. et al. Preimplantation genetic haplotyping: 127 diagnostic cycles demonstrating a robust, efficient alternative to direct mutation testing on single cells. Reprod Biomed Online. 2010; 20 (4): 470-476.Van de Velde H., De Rycke M., De Man C. et al. The experience of two European preimplantation genetic diagnosis centres on human leukocyte antigen typing. Hum Reprod 2009; 24 (3): 732-740.Hellani A., Coskun S., Tbakhi A. et al. Clinical application of multiple displacement amplification in preimplantation genetic diagnosis. Reprod Biomed Online 2005; 10: 376-380.Renwick P.J., Trussler J., Ostad-Saffari E. et al. Proof of principle and first cases using preimplantation genetic haplotyping - a paradigm shift for embryo diagnosis. Reprod Biomed Online 2006; 13: 110-119.Norwitz E.R., Levy B. Noninvasive Prenatal Testing: The future is now. Rev Obstet Gynecol 2013; 6 (2): 48-62.Dolan C.R., Smith L.T., Sybert V.P. Prenatal detection ofepidermolysis bullosa letalis and pyloric atresia in a fetus by abnormal ultrasound and elevated a-fetoprotein. Am J Med Genet 1993; 47: 395-400.Sonek J. First trimester ultrasonography in screening and detection of fetal anomalies. Am J Med Genet C Semin Med Genet 2007; 145: 45-61.Karetnikova N.A., Goncharova E.A., Stygar A.M. et al. Current possibilities of genetic pathology diagnosis in early pregnancy. Russian Journal of Human Reproduction 2010; 2: 82-86.Lo Y.M., Chan K.C., Sun H. et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2010; 2(61): 61ra91.Sparks A.B., Wang E.T., Struble C.A. et al. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat Diagn 2012; 32 (1): 3-9.Sparks A.B., Struble C.A., Wang E.T. et al. Non-invasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 206 (4): 319.e1-9.Ashoor G., Syngelaki A., Wagner M. et al. Chromosome-selective sequencing of maternal plasma cell-free DNA for first trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 206 (4): 322.e1-5.Norton M., Brar H., Weiss J et al. Non-invasive Chromosomal Evaluation (NICE) Study: results of a multicenter, prospective, cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 207 (2): 137.e1-8.Nicolaides K.H., Syngelaki A., Ashoor G. et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population.Am J Obstet Gynecol 2012; 207: 374.e1-6.Ashoor G., Syngelaki A., Nicolaides K.H. et al. Trisomy 13 detection in the first trimester of pregnancy using a chromosome-selective cell-free DNA analysis method. Ultrasound Obstet Gynecol 2013; 41 (1): 21-25.Tounta G., Kolialexi A., Papantoniou N. et al. Non-invasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma: progress overview beyond predictive and personalized diagnosis. EPMA J 2011; 2 (2): 163-171.