{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:03:31Z","timestamp":1776272611646,"version":"3.50.1"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome is a rare disease, characterised by the aplasia of vagina and uterus in women with a 46,XX karyotype. Most cases are sporadic, but familial recurrence has also been described. Herein, we investigated an Italian cohort of 36 unrelated MRKH patients to explore the presence of pathogenic copy number variations (CNVs) by array-CGH and MLPA assays. On the whole, aberrations were found in 9\/36 (25%) patients. Interestingly, one patient showed a novel heterozygous microduplication at Xp22.33, not yet described in MRKH patients, containing the <jats:italic>PRKX<\/jats:italic> gene. Moreover, a novel duplication of a specific <jats:italic>SHOX<\/jats:italic> enhancer was highlighted by MLPA. To predict the potential significance of CNVs in MRKH pathogenesis, we provided a network analysis for protein-coding genes found in the altered genomic regions. Although not all of these genes taken individually showed a clear clinical significance, their combination in a computational network highlighted that the most relevant biological connections are related to the anatomical structure development. In conclusion, the results described in the present study identified novel genetic alterations and interactions that may be likely involved in MRKH phenotype determination, so adding new insights into the complex puzzle of MRKH disease.<\/jats:p>","DOI":"10.1038\/s41598-020-79827-5","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T11:49:18Z","timestamp":1610365758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protein\u2013protein interaction network analysis applied to DNA copy number profiling suggests new perspectives on the aetiology of Mayer\u2013Rokitansky\u2013K\u00fcster\u2013Hauser syndrome"],"prefix":"10.1038","volume":"11","author":[{"given":"Paola","family":"Pontecorvi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Capalbo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Ceccarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Megiorni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrica","family":"Vescarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Bottillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Preziosi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Fabbretti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Perniola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierluigi","family":"Benedetti Panici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Pizzuti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-8917","authenticated-orcid":false,"given":"Cinzia","family":"Marchese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"79827_CR1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/S0022-3476(79)80514-4","volume":"95","author":"PA Duncan","year":"1979","unstructured":"Duncan, P. A., Shapiro, L. R., Stangel, J. J., Klein, R. M. & Addonizio, J. C. The MURCS association: M\u00fcllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia. J. Pediatr. 95, 399\u2013402 (1979).","journal-title":"J. Pediatr."},{"key":"79827_CR2","first-page":"192","volume":"3","author":"EH Str\u00fcbbe","year":"1994","unstructured":"Str\u00fcbbe, E. H., Cremers, C. W., Willemsen, W. N., Rolland, R. & Thijn, C. J. The Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome without and with associated features: two separate entities?. Clin. Dysmorphol. 3, 192\u2013199 (1994).","journal-title":"Clin. Dysmorphol."},{"key":"79827_CR3","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/cge.12883","volume":"91","author":"L Fontana","year":"2017","unstructured":"Fontana, L., Gentilin, B., Fedele, L., Gervasini, C. & Miozzo, M. Genetics of Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome. Clin. Genet. 91, 233\u2013246 (2017).","journal-title":"Clin. Genet."},{"key":"79827_CR4","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S0015-0282(01)02943-0","volume":"77","author":"JJ Gorgojo","year":"2002","unstructured":"Gorgojo, J. J., Almod\u00f3var, F., L\u00f3pez, E. & Donnay, S. Gonadal agenesis 46, XX associated with the atypical form of Rokitansky syndrome. Fertil. Steril. 77, 185\u2013187 (2002).","journal-title":"Fertil. Steril."},{"key":"79827_CR5","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.jpag.2008.11.006","volume":"22","author":"EJ Bean","year":"2009","unstructured":"Bean, E. J., Mazur, T. & Robinson, A. D. Mayer-Rokitansky-K\u00fcster-Hauser syndrome: Sexuality, psychological effects, and quality of life. J. Pediatr. Adolesc. Gynecol. 22, 339\u2013346 (2009).","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"79827_CR6","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1007\/s00404-017-4372-2","volume":"295","author":"S Choussein","year":"2017","unstructured":"Choussein, S., Nasioudis, D., Schizas, D. & Economopoulos, K. P. Mullerian dysgenesis: a critical review of the literature. Arch Gynecol Obstet 295, 1369\u20131381 (2017).","journal-title":"Arch Gynecol Obstet"},{"key":"79827_CR7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ijgo.2007.03.012","volume":"98","author":"F Borruto","year":"2007","unstructured":"Borruto, F., Camoglio, F. S., Zampieri, N. & Fedele, L. The laparoscopic Vecchietti technique for vaginal agenesis. Int. J. Gynaecol. Obstet. 98, 15\u201319 (2007).","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"79827_CR8","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1097\/01.prs.0000435844.95551.35","volume":"133","author":"LA Dessy","year":"2014","unstructured":"Dessy, L. A. et al. The use of cultured autologous oral epithelial cells for vaginoplasty in male-to-female transsexuals: A feasibility, safety, and advantageousness clinical pilot study. Plast. Reconstr. Surg. 133, 158\u2013161 (2014).","journal-title":"Plast. Reconstr. Surg."},{"key":"79827_CR9","doi-asserted-by":"publisher","first-page":"865","DOI":"10.2147\/IJWH.S75637","volume":"7","author":"L Londra","year":"2015","unstructured":"Londra, L., Chuong, F. S. & Kolp, L. Mayer-Rokitansky-Kuster-Hauser syndrome: A review. Int. J. Womens Health 7, 865\u2013870 (2015).","journal-title":"Int. J. Womens Health"},{"key":"79827_CR10","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.jmig.2014.09.012","volume":"22","author":"P Benedetti Panici","year":"2015","unstructured":"Benedetti Panici, P. et al. Autologous in vitro cultured vaginal tissue for vaginoplasty in women with Mayer-Rokitansky-K\u00fcster-Hauser syndrome: anatomic and functional results. J. Minim. Invasive Gynecol. 22, 205\u2013211 (2015).","journal-title":"J. Minim. Invasive Gynecol."},{"key":"79827_CR11","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1093\/humrep\/13.6.1470","volume":"13","author":"Z Ben-Rafael","year":"1998","unstructured":"Ben-Rafael, Z., Bar-Hava, I., Levy, T. & Orvieto, R. Simplifying ovulation induction for surrogacy in women with Mayer-Rokitansky-Kuster-Hauser syndrome. Hum. Reprod. 13, 1470\u20131471 (1998).","journal-title":"Hum. Reprod."},{"key":"79827_CR12","doi-asserted-by":"publisher","first-page":"2326","DOI":"10.1093\/humrep\/15.11.2326","volume":"15","author":"S Beski","year":"2000","unstructured":"Beski, S., Gorgy, A., Venkat, G., Craft, I. L. & Edmonds, K. Gestational surrogacy: a feasible option for patients with Rokitansky syndrome. Hum Reprod 15, 2326\u20132328 (2000).","journal-title":"Hum Reprod"},{"key":"79827_CR13","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/S0140-6736(14)61728-1","volume":"385","author":"M Br\u00e4nnstr\u00f6m","year":"2015","unstructured":"Br\u00e4nnstr\u00f6m, M. et al. Livebirth after uterus transplantation. Lancet 385, 607\u2013616 (2015).","journal-title":"Lancet"},{"key":"79827_CR14","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.fertnstert.2016.04.001","volume":"106","author":"M Br\u00e4nnstr\u00f6m","year":"2016","unstructured":"Br\u00e4nnstr\u00f6m, M. et al. One uterus bridging three generations: first live birth after mother-to-daughter uterus transplantation. Fertil. Steril. 106, 261\u2013266 (2016).","journal-title":"Fertil. Steril."},{"key":"79827_CR15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.rbmo.2015.09.006","volume":"32","author":"S Friedler","year":"2016","unstructured":"Friedler, S. et al. The reproductive potential of patients with Mayer-Rokitansky-K\u00fcster-Hauser syndrome using gestational surrogacy: a systematic review. Reprod. Biomed. Online 32, 54\u201361 (2016).","journal-title":"Reprod. Biomed. Online"},{"key":"79827_CR16","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.apjr.2016.06.005","volume":"5","author":"M Ferjaoui","year":"2016","unstructured":"Ferjaoui, M. et al. Spontaneous pregnancy after vaginoplasty in a patient presenting a congenital vaginal aplasia. Asian Pac. J. Reprod. 5, 351\u2013353 (2016).","journal-title":"Asian Pac. J. Reprod."},{"key":"79827_CR17","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.fertnstert.2014.10.053","volume":"103","author":"K Rall","year":"2015","unstructured":"Rall, K. et al. Mayer-Rokitansky-K\u00fcster-Hauser syndrome discordance in monozygotic twins: matrix metalloproteinase 14, low-density lipoprotein receptor-related protein 10, extracellular matrix, and neoangiogenesis genes identified as candidate genes in a tissue-specific mosaicism. Fertil. Steril. 103, 494-502.e3 (2015).","journal-title":"Fertil. Steril."},{"key":"79827_CR18","doi-asserted-by":"publisher","first-page":"817","DOI":"10.3109\/01443615.2016.1157149","volume":"36","author":"X Ma","year":"2016","unstructured":"Ma, X. et al. Familial occurrence of Mayer-Rokitansky-K\u00fcster-Hauser syndrome. J. Obstet. Gynaecol. 36, 817\u2013818 (2016).","journal-title":"J. Obstet. Gynaecol."},{"key":"79827_CR19","first-page":"147","volume":"14","author":"MH Shokeir","year":"1978","unstructured":"Shokeir, M. H. Aplasia of the M\u00fcllerian system: evidence for probable sex-limited autosomal dominant inheritance. Birth Defects Orig. Artic Ser. 14, 147\u2013165 (1978).","journal-title":"Birth Defects Orig. Artic Ser."},{"key":"79827_CR20","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1750-1172-6-32","volume":"6","author":"K Rall","year":"2011","unstructured":"Rall, K. et al. A combination of transcriptome and methylation analyses reveals embryologically-relevant candidate genes in MRKH patients. Orphanet. J. Rare Dis. 6, 32 (2011).","journal-title":"Orphanet. J. Rare Dis."},{"key":"79827_CR21","doi-asserted-by":"publisher","first-page":"e91010","DOI":"10.1371\/journal.pone.0091010","volume":"9","author":"C Nodale","year":"2014","unstructured":"Nodale, C. et al. Gene expression profile of patients with Mayer-Rokitansky-K\u00fcster-Hauser syndrome: new insights into the potential role of developmental pathways. PLoS ONE 9, e91010 (2014).","journal-title":"PLoS ONE"},{"key":"79827_CR22","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/nrg3871","volume":"16","author":"M Zarrei","year":"2015","unstructured":"Zarrei, M., MacDonald, J. R., Merico, D. & Scherer, S. W. A copy number variation map of the human genome. Nat. Rev. Genet. 16, 172\u2013183 (2015).","journal-title":"Nat. Rev. Genet."},{"key":"79827_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ejhg.2011.158","volume":"20","author":"K Morcel","year":"2012","unstructured":"Morcel, K. et al. Clinical utility gene card for: Mayer-Rokitansky-K\u00fcster-Hauser syndrome. Eur. J. Hum. Genet. 20, 1\u20133 (2012).","journal-title":"Eur. J. Hum. Genet."},{"key":"79827_CR24","first-page":"3","volume":"30","author":"S Ledig","year":"2018","unstructured":"Ledig, S. & Wieacker, P. Clinical and genetic aspects of Mayer-Rokitansky-K\u00fcster-Hauser syndrome. Med. Genet. 30, 3\u201311 (2018).","journal-title":"Med. Genet."},{"key":"79827_CR25","doi-asserted-by":"publisher","first-page":"e1002820","DOI":"10.1371\/journal.pcbi.1002820","volume":"8","author":"DY Cho","year":"2012","unstructured":"Cho, D. Y., Kim, Y. A. & Przytycka, T. M. Network biology approach to complex diseases. PLoS Comput. Biol. 8, e1002820 (2012).","journal-title":"PLoS Comput. Biol."},{"key":"79827_CR26","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1097\/GIM.0b013e3182217a3a","volume":"13","author":"HM Kearney","year":"2011","unstructured":"Kearney, H. M. et al. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet. Med. 13, 680\u2013685 (2011).","journal-title":"Genet. Med."},{"key":"79827_CR27","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"79827_CR28","doi-asserted-by":"publisher","first-page":"D433","DOI":"10.1093\/nar\/gki005","volume":"33","author":"C von Mering","year":"2005","unstructured":"von Mering, C. et al. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res. 33, D433\u2013D437 (2005).","journal-title":"Nucleic Acids Res."},{"key":"79827_CR29","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk, D. et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47, D607\u2013D613 (2019).","journal-title":"Nucleic Acids Res"},{"key":"79827_CR30","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"79827_CR31","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1093\/bioinformatics\/btp517","volume":"25","author":"G Scardoni","year":"2009","unstructured":"Scardoni, G., Petterlini, M. & Laudanna, C. Analyzing biological network parameters with CentiScaPe. Bioinformatics 25, 2857\u20132859 (2009).","journal-title":"Bioinformatics"},{"key":"79827_CR32","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2105-4-2","volume":"4","author":"GD Bader","year":"2003","unstructured":"Bader, G. D. & Hogue, C. W. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform. 4, 2 (2003).","journal-title":"BMC Bioinform."},{"key":"79827_CR33","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1021\/acs.jproteome.8b00702","volume":"18","author":"NT Doncheva","year":"2019","unstructured":"Doncheva, N. T., Morris, J. H., Gorodkin, J. & Jensen, L. J. Cytoscape StringApp: Network analysis and visualization of proteomics data. J. Proteome Res. 18, 623\u2013632 (2019).","journal-title":"J. Proteome Res."},{"key":"79827_CR34","doi-asserted-by":"publisher","first-page":"9260","DOI":"10.1073\/pnas.132051799","volume":"99","author":"X Li","year":"2002","unstructured":"Li, X. et al. PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis. Proc. Natl. Acad. Sci. USA 99, 9260\u20139265 (2002).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"79827_CR35","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/1750-1172-6-53","volume":"6","author":"M Sandbacka","year":"2011","unstructured":"Sandbacka, M., Halttunen, M., Jokimaa, V., Aittomaki, K. & Laivuori, H. Evaluation of SHOX copy number variations in patients with Mullerian aplasia. Orphanet. J. Rare Dis. 6, 53 (2011).","journal-title":"Orphanet. J. Rare Dis."},{"key":"79827_CR36","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1097\/GIM.0b013e3181ed6185","volume":"12","author":"C Gervasini","year":"2010","unstructured":"Gervasini, C. et al. SHOX duplications found in some cases with type I Mayer-Rokitansky-Kuster-Hauser syndrome. Genet. Med. 12, 634\u2013640 (2010).","journal-title":"Genet. Med."},{"key":"79827_CR37","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/j.1399-0004.1993.tb04420.x","volume":"43","author":"J Battin","year":"1993","unstructured":"Battin, J., Lacombe, D. & Leng, J. J. Familial occurrence of hereditary renal adysplasia with m\u00fcllerian anomalies. Clin. Genet. 43, 23\u201324 (1993).","journal-title":"Clin. Genet."},{"key":"79827_CR38","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1756-0381-4-10","volume":"4","author":"GA Pavlopoulos","year":"2011","unstructured":"Pavlopoulos, G. A. et al. Using graph theory to analyze biological networks. BioData Min. 4, 10 (2011).","journal-title":"BioData Min."},{"key":"79827_CR39","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1136\/jmg.2007.051839","volume":"45","author":"C Cheroki","year":"2008","unstructured":"Cheroki, C. et al. Genomic imbalances associated with mullerian aplasia. J. Med. Genet. 45, 228\u2013232 (2008).","journal-title":"J. Med. Genet."},{"key":"79827_CR40","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1750-1172-4-25","volume":"4","author":"L Bernardini","year":"2009","unstructured":"Bernardini, L. et al. Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports. Orphanet. J. Rare Dis. 4, 25 (2009).","journal-title":"Orphanet. J. Rare Dis."},{"key":"79827_CR41","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1016\/j.fertnstert.2010.07.1062","volume":"95","author":"S Ledig","year":"2011","unstructured":"Ledig, S. et al. Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-K\u00fcster-Hauser syndrome. Fertil. Steril. 95, 1589\u20131594 (2011).","journal-title":"Fertil. Steril."},{"key":"79827_CR42","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1136\/jmg.2010.082412","volume":"48","author":"S Nik-Zainal","year":"2011","unstructured":"Nik-Zainal, S. et al. High incidence of recurrent copy number variants in patients with isolated and syndromic M\u00fcllerian aplasia. J. Med. Genet. 48, 197\u2013204 (2011).","journal-title":"J. Med. Genet."},{"key":"79827_CR43","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1750-1172-8-125","volume":"8","author":"M Sandbacka","year":"2013","unstructured":"Sandbacka, M. et al. TBX6, LHX1 and copy number variations in the complex genetics of M\u00fcllerian aplasia. Orphanet. J. Rare Dis. 8, 125 (2013).","journal-title":"Orphanet. J. Rare Dis."},{"key":"79827_CR44","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1242\/dev.00951","volume":"131","author":"A Kobayashi","year":"2004","unstructured":"Kobayashi, A., Shawlot, W., Kania, A. & Behringer, R. R. Requirement of Lim1 for female reproductive tract development. Development 131, 539\u2013549 (2004).","journal-title":"Development"},{"key":"79827_CR45","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1242\/dev.01858","volume":"132","author":"A Kobayashi","year":"2005","unstructured":"Kobayashi, A. et al. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development 132, 2809\u20132823 (2005).","journal-title":"Development"},{"key":"79827_CR46","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.ydbio.2005.09.027","volume":"288","author":"A Pedersen","year":"2005","unstructured":"Pedersen, A., Skjong, C. & Shawlot, W. Lim 1 is required for nephric duct extension and ureteric bud morphogenesis. Dev. Biol. 288, 571\u2013581 (2005).","journal-title":"Dev. Biol."},{"key":"79827_CR47","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1159\/000108929","volume":"1","author":"J Klattig","year":"2007","unstructured":"Klattig, J. & Englert, C. The M\u00fcllerian duct: recent insights into its development and regression. Sex Dev. 1, 271\u2013278 (2007).","journal-title":"Sex Dev."},{"key":"79827_CR48","doi-asserted-by":"publisher","first-page":"e310","DOI":"10.1002\/wdev.310","volume":"7","author":"ZY Roly","year":"2018","unstructured":"Roly, Z. Y. et al. The cell biology and molecular genetics of M\u00fcllerian duct development. Wiley Interdiscip. Rev. Dev. Biol. 7, e310 (2018).","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"79827_CR49","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1093\/biolre\/ioy160","volume":"100","author":"G St-Jean","year":"2019","unstructured":"St-Jean, G. et al. Targeted ablation of Wnt4 and Wnt5a in M\u00fcllerian duct mesenchyme impedes endometrial gland development and causes partial M\u00fcllerian agenesis. Biol. Reprod. 100, 49\u201360 (2019).","journal-title":"Biol. Reprod."},{"key":"79827_CR50","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1046>3.0.CO;2-9","volume":"219","author":"S Nacke","year":"2000","unstructured":"Nacke, S., Sch\u00e4fer, R., Habr\u00e9 de Angelis, M. & Mundlos, S. Mouse mutant \u201crib-vertebrae\u201d (rv): a defect in somite polarity. Dev. Dyn. 219, 192\u2013200 (2000).","journal-title":"Dev. Dyn."},{"key":"79827_CR51","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1242\/dev.00367","volume":"130","author":"PH White","year":"2003","unstructured":"White, P. H., Farkas, D. R., McFadden, E. E. & Chapman, D. L. Defective somite patterning in mouse embryos with reduced levels of Tbx6. Development 130, 1681\u20131690 (2003).","journal-title":"Development"},{"key":"79827_CR52","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1159\/000096235","volume":"1","author":"T Svingen","year":"2007","unstructured":"Svingen, T. & Koopman, P. Involvement of homeobox genes in mammalian sexual development. Sex Dev 1, 12\u201323 (2007).","journal-title":"Sex Dev"},{"key":"79827_CR53","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1002\/dvdy.24482","volume":"246","author":"DR Rux","year":"2017","unstructured":"Rux, D. R. & Wellik, D. M. Hox genes in the adult skeleton: Novel functions beyond embryonic development. Dev. Dyn. 246, 310\u2013317 (2017).","journal-title":"Dev. Dyn."},{"key":"79827_CR54","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.bbadis.2009.03.001","volume":"1792","author":"G Aguiari","year":"2009","unstructured":"Aguiari, G. et al. Deficiency of polycystic kidney disease-1 gene (PKD1) expression increases A(3) adenosine receptors in human renal cells: implications for cAMP-dependent signalling and proliferation of PKD1-mutated cystic cells. Biochim. Biophys. Acta 1792, 531\u2013540 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"79827_CR55","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1093\/hmg\/6.11.1985","volume":"6","author":"K Schiebel","year":"1997","unstructured":"Schiebel, K. et al. Abnormal XY interchange between a novel isolated protein kinase gene, PRKY, and its homologue, PRKX, accounts for one third of all (Y+)XX males and (Y-)XY females. Hum. Mol. Genet. 6, 1985\u20131989 (1997).","journal-title":"Hum. Mol. Genet."},{"key":"79827_CR56","doi-asserted-by":"publisher","first-page":"5370","DOI":"10.1074\/jbc.274.9.5370","volume":"274","author":"B Zimmermann","year":"1999","unstructured":"Zimmermann, B., Chiorini, J. A., Ma, Y., Kotin, R. M. & Herberg, F. W. PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase regulated by the regulatory subunit type I. J. Biol. Chem. 274, 5370\u20135378 (1999).","journal-title":"J. Biol. Chem."},{"key":"79827_CR57","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.1681\/ASN.2005030240","volume":"16","author":"X Li","year":"2005","unstructured":"Li, X. et al. Protein kinase X activates ureteric bud branching morphogenesis in developing mouse metanephric kidney. J. Am. Soc. Nephrol. 16, 3543\u20133552 (2005).","journal-title":"J. Am. Soc. Nephrol."},{"key":"79827_CR58","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/ki.2009.95","volume":"76","author":"X Li","year":"2009","unstructured":"Li, X. et al. Protein kinase-X interacts with Pin-1 and Polycystin-1 during mouse kidney development. Kidney Int. 76, 54\u201362 (2009).","journal-title":"Kidney Int."},{"key":"79827_CR59","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/jcb.25304","volume":"117","author":"S Huang","year":"2016","unstructured":"Huang, S., Li, Q., Alberts, I. & Li, X. PRKX, a Novel cAMP-dependent protein kinase member, plays an important role in development. J. Cell. Biochem. 117, 566\u2013573 (2016).","journal-title":"J. Cell. Biochem."},{"key":"79827_CR60","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.diff.2017.08.002","volume":"97","author":"SJ Robboy","year":"2017","unstructured":"Robboy, S. J., Kurita, T., Baskin, L. & Cunha, G. R. New insights into human female reproductive tract development. Differentiation 97, 9\u201322 (2017).","journal-title":"Differentiation"},{"key":"79827_CR61","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/nrg1225","volume":"4","author":"A Kobayashi","year":"2003","unstructured":"Kobayashi, A. & Behringer, R. R. Developmental genetics of the female reproductive tract in mammals. Nat. Rev. Genet. 4, 969\u2013980 (2003).","journal-title":"Nat. Rev. Genet."},{"key":"79827_CR62","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/nrneph.2015.140","volume":"11","author":"N Nicolaou","year":"2015","unstructured":"Nicolaou, N., Renkema, K. Y., Bongers, E. M., Giles, R. H. & Knoers, N. V. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat. Rev. Nephrol. 11, 720\u2013731 (2015).","journal-title":"Nat. Rev. Nephrol."},{"key":"79827_CR63","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1093\/humrep\/dem096","volume":"22","author":"PB Panici","year":"2007","unstructured":"Panici, P. B. et al. Vaginoplasty using autologous in vitro cultured vaginal tissue in a patient with Mayer-von-Rokitansky-Kuster-Hauser syndrome. Hum. Reprod. 22, 2025\u20132028 (2007).","journal-title":"Hum. Reprod."},{"key":"79827_CR64","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1055\/s-0030-1268703","volume":"29","author":"PB Panici","year":"2011","unstructured":"Panici, P. B. et al. Vaginal reconstruction with the Abb\u00e8-McIndoe technique: from dermal grafts to autologous in vitro cultured vaginal tissue transplant. Semin. Reprod. Med. 29, 45\u201354 (2011).","journal-title":"Semin. Reprod. Med."},{"key":"79827_CR65","doi-asserted-by":"publisher","first-page":"201518","DOI":"10.1155\/2014\/201518","volume":"2014","author":"C Nodale","year":"2014","unstructured":"Nodale, C. et al. Characterization of human vaginal mucosa cells for autologous in vitro cultured vaginal tissue transplantation in patients with MRKH syndrome. Biomed. Res. Int. 2014, 201518 (2014).","journal-title":"Biomed. Res. Int."},{"key":"79827_CR66","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/1471-0528.15477","volume":"126","author":"I Sabatucci","year":"2019","unstructured":"Sabatucci, I. et al. Treatment of the Mayer-Rokitansky-K\u00fcster-Hauser syndrome with autologous in vitro cultured vaginal tissue: descriptive study of long-term results and patient outcomes. BJOG 126, 123\u2013127 (2019).","journal-title":"BJOG"},{"key":"79827_CR67","doi-asserted-by":"publisher","first-page":"572281","DOI":"10.3389\/fcell.2020.572281","volume":"8","author":"T Hentrich","year":"2020","unstructured":"Hentrich, T. et al. The endometrial transcription landscape of MRKH syndrome. Front. Cell Dev. Biol. 8, 572281 (2020).","journal-title":"Front. Cell Dev. Biol."},{"key":"79827_CR68","first-page":"65","volume":"1","author":"I Lobo","year":"2008","unstructured":"Lobo, I. Copy number variation and genetic disease. Nat. Educ. 1, 65 (2008).","journal-title":"Nat. Educ."},{"key":"79827_CR69","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1159\/000494896","volume":"13","author":"B Backhouse","year":"2019","unstructured":"Backhouse, B. et al. Identification of candidate genes for Mayer\u2013Rokitansky\u2013K\u00fcster\u2013Hauser syndrome using genomic approaches. Sex Dev. 13, 26\u201334 (2019).","journal-title":"Sex Dev."},{"key":"79827_CR70","doi-asserted-by":"publisher","first-page":"100089","DOI":"10.1016\/j.eurox.2019.100089","volume":"4","author":"HX Pan","year":"2019","unstructured":"Pan, H. X. et al. Detection of. Eur. J. Obstet. Gynecol. Reprod. Biol. X 4, 100089 (2019).","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol. X"},{"key":"79827_CR71","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1093\/humrep\/dez126","volume":"34","author":"MK Herlin","year":"2019","unstructured":"Herlin, M. K. et al. Whole-exome sequencing identifies a GREB1L variant in a three-generation family with M\u00fcllerian and renal agenesis: a novel candidate gene in Mayer\u2013Rokitansky\u2013K\u00fcster\u2013Hauser (MRKH) syndrome. A case report. Hum. Reprod. 34, 1838\u20131846 (2019).","journal-title":"Hum. Reprod."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79827-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79827-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79827-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T01:41:55Z","timestamp":1670031715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-79827-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["79827"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-79827-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"assertion":[{"value":"11 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"448"}}