Zusammenfassung
Genodermatosen sind seltene genetische Erkrankungen mit einem breiten Spektrum an kutanen und extrakutanen Manifestationen und molekulargenetischem Hintergrund. Bei Verdacht auf eine Genodermatose bleiben die klinische Bewertung durch erfahrene Spezialisten und eine sinnvolle Staffelung der Untersuchungen auch in der Ära der „Next Generation Sequencing“ (NGS) unabdingbar. Der Diagnostikpfad zur molekularen Abklärung der Diagnose ist von der klinischen und genetischen Heterogenität der Krankheitsgruppe abhängig. Die Anwendung der NGS-basierten Tests führt zu einer wesentlich kürzeren Zeit der Diagnose der Genodermatosen und der Identifizierung neuer Erkrankungen und krankheitsassoziierter Gene. Die neu gewonnenen Erkenntnisse zu Genotyp-Phänotyp-Korrelationen sollten die Grundlage für eine zeitgemäße molekulargenetische Revision der Klassifikation der Genodermatosen bilden.
Abstract
Genodermatoses are rare genetic disorders with a broad spectrum of cutaneous and extracutaneous manifestations that have a genetic background. A thorough clinical examination, laboratory workup and morphological analyses of the skin remain crucial for the diagnosis in the era of next generation sequencing (NGS). The diagnostic algorithm depends on the clinical and molecular heterogeneity and should be adapted for each group of genodermatoses. In cases with uncharacteristic phenotypes which cannot be classified, NGS-based testing accelerates the time to diagnosis and leads to the identification of new disorders and new disease-associated genes. The new knowledge on genotype–phenotype correlations should enable revision of the classification of genodermatoses on a molecular basis.
Literatur
Leech SN, Moss C (2007) A current and online genodermatosis database. Br J Dermatol 156(6):1115–1148
Feramisco JD, Sadreyev RI, Murray ML, Grishin NV, Tsao H (2009) Phenotypic and genotypic analyses of genetic skin disease through the Online Mendelian Inheritance in Man (OMIM) database. J Invest Dermatol 129(11):2628–2636
Lemke JR, Kernland-Lang K, Hörtnagel K, Itin P (2014) Monogenic human skin disorders. Dermatology 229(2):55–64
Has C, Giehl K (2014) [Rare diseases are common]. Hautarzt 65(6):488–489
Has C, Bruckner-Tuderman L (2014) The genetics of skin fragility. Annu Rev Genomics Hum Genet 15:245–268
Laimer M, Bauer JW, Lang R (2015) [Molecular diagnostics in genodermatoses]. Hautarzt 66(3):203–211. (quiz 212–3)
Pohla-Gubo G, Cepeda-Valdes R, Hintner H (2010) Immunofluorescence mapping for the diagnosis of epidermolysis bullosa. Dermatol Clin 28(2):201–210, vii
Has C, Kiritsi D (2014) [The many facets of inherited skin fragility]. Hautarzt 65(6):490–498
Lehmann J, Schubert S, Emmert S (2014) Xeroderma pigmentosum: diagnostic procedures, interdisciplinary patient care, and novel therapeutic approaches. J Dtsch Dermatol Ges J Ger Soc Dermatol 12(10):867–872
Lehmann J, Schubert S, Schäfer A, Laspe P, Haenssle HA, Ohlenbusch A et al (2014) A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.12841
Poblete-Gutiérrez P, Wiederholt T, Merk HF, Frank J (2006) [Laboratory tests and therapeutic strategies for the porphyrias]. Hautarzt 57(6):493–501
Poblete-Gutiérrez P, Wiederholt T, Merk HF, Frank J (2006) The porphyrias: clinical presentation, diagnosis and treatment. Eur J Dermatol 16(3):230–240
Traupe H, Fischer J, Oji V (2014) Nonsyndromic types of ichthyoses – an update. J Dtsch Dermatol Ges 12(2):109–121
Raghunath M, Hennies HC, Velten F, Wiebe V, Steinert PM, Reis A et al (1998) A novel in situ method for the detection of deficient transglutaminase activity in the skin. Arch Dermatol Res 290(11):621–627
Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E et al (2010) Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol 63(4):607–641
Fischer J (2009) Autosomal recessive congenital ichthyosis. J Invest Dermatol 129(6):1319–1321
Israeli S, Goldberg I, Fuchs-Telem D, Bergman R, Indelman M, Bitterman-Deutsch O et al (2013) Non-syndromic autosomal recessive congenital ichthyosis in the Israeli population. Clin Exp Dermatol 38(8):911–916
Tenedini E, Artuso L, Bernardis I, Artusi V, Percesepe A, De Rosa L et al (2015) Amplicon-based next-generation sequencing: an effective approach for the molecular diagnosis of epidermolysis bullosa. Br J Dermatol 173(3):731–738
Scott CA, Plagnol V, Nitoiu D, Bland PJ, Blaydon DC, Chronnell CM et al (2013) Targeted sequence capture and high-throughput sequencing in the molecular diagnosis of ichthyosis and other skin diseases. J Invest Dermatol 133(2):573–576
Has C, Kiritsi D, Mellerio JE, Franzke C-W, Wedgeworth E, Tantcheva-Poor I et al (2014) The missense mutation p.R1303Q in type XVII collagen underlies junctional epidermolysis bullosa resembling Kindler syndrome. J Invest Dermatol 134(3):845–849
Salam A, Simpson MA, Stone KL, Takeichi T, Nanda A, Akiyama M et al (2014) Next generation diagnostics of heritable connective tissue disorders. Matrix Biol J Int Soc Matrix Biol 33:35–40
Takeichi T, Liu L, Fong K, Ozoemena L, McMillan JR, Salam A et al (2015) Whole-exome sequencing improves mutation detection in a diagnostic epidermolysis bullosa laboratory. Br J Dermatol 172(1):94–100
Kiritsi D, Valari M, Fortugno P, Hausser I, Lykopoulou L, Zambruno G et al (2015) Whole-exome sequencing in patients with ichthyosis reveals modifiers associated with increased IgE levels and allergic sensitizations. J Allergy Clin Immunol 135(1):280–283
Campbell P, Morton PE, Takeichi T, Salam A, Roberts N, Proudfoot LE et al (2014) Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR. J Invest Dermatol 134(10):2570–2578
Takeichi T, Nanda A, Aristodemou S, McMillan JR, Lee J, Akiyama M et al (2015) Whole-exome sequencing diagnosis of two autosomal recessive disorders in one family. Br J Dermatol 172(5):1407–1411
Pohler E, Cunningham F, Sandilands A, Cole C, Digby S, McMillan JR et al (2015) Novel autosomal dominant mutation in loricrin presenting as prominent ichthyosis. Br J Dermatol. doi:10.1111/bjd.13895
Giehl KA, Eckstein GN, Pasternack SM, Praetzel-Wunder S, Ruzicka T, Lichtner P et al (2012) Nonsense mutations in AAGAB cause punctate palmoplantar keratoderma type Buschke-Fischer-Brauer. Am J Hum Genet 91(4):754–759
Blaydon DC, Lind LK, Plagnol V, Linton KJ, Smith FJD, Wilson NJ et al (2013) Mutations in AQP5, encoding a water-channel protein, cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma. Am J Hum Genet 93(2):330–335
Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A, Isakov O et al (2013) Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet 45(10):1244–1248
McAleer MA, Pohler E, Smith FJD, Wilson NJ, Cole C, MacGowan S et al (2015) Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin. J Allergy Clin Immunol. doi:10.1016/j.jaci.2015.05.002
Happle R (2014) [How frequently does genetic mosaicism occur in the skin?]. Hautarzt 65(6):536–541
Has C (2011) Mosaicism in the skin: the importance of mild or minimal skin lesions. Arch Dermatol 147(9):1094–1096
Hoffman K, Hertl M, Sitaru C (2015) Molekulare Diagnostik der blasenbildenden Autoimmundermatosen. Hautarzt. doi:10.1007/s105-015-3723-9
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Has, C., He, Y. Praktische Aspekte der molekularen Diagnostik bei Genodermatosen. Hautarzt 67, 53–58 (2016). https://doi.org/10.1007/s00105-015-3721-y
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DOI: https://doi.org/10.1007/s00105-015-3721-y