{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:48Z","timestamp":1753869408574,"version":"3.41.2"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,16]],"date-time":"2020-02-16T00:00:00Z","timestamp":1581811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CB2015\u2010254883"],"award-info":[{"award-number":["CB2015\u2010254883"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Focal dermal hypoplasia (FDH) is rare X\u2010linked dominant disease characterized by atrophy and linear pigmentation of the skin, split hand\/foot deformities and ocular anomalies. FDH is caused by mutations of the Porcupine (<jats:italic>PORCN<\/jats:italic>) gene, which encodes an enzyme that catalyzes the palmitoylation of Wnt ligands required for their secretion. High resolution melting analysis (HRM) is a technique that allows rapid, labor\u2010efficient, low\u2010cost detection of genomic variants. In the present study, we report the successful implementation of HRM in the molecular diagnosis of FDH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Polymerase chain reaction and HRM assays were designed and optimized for each of the coding exons of the <jats:italic>PORCN<\/jats:italic> gene, processing genomic DNA samples form a non\u2010affected control and a patient complying with the FDH diagnostic criteria. The causal mutation was characterized by Sanger sequencing from an amplicon showing a HRM trace suggesting heterozygous variation and was validated using an amplification\u2010refractory mutation system (ARMS) assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The melting profiles suggested the presence of a variant in the patient within exon 1. Sanger sequencing revealed a previously unknown C to T transition replacing a glutamine codon for a premature stop codon at position 28, which was validated using ARMS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Next\u2010generation sequencing facilitates the molecular diagnosis of monogenic disorders; however, its cost\u2013benefit ratio is not optimal when a single, small or medium size causal gene is already identified and the clinical diagnostic presumption is strong. Under those conditions, as it is the case for FDH, HRM represents a cost\u2010 and labor\u2010effective approach.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3165","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T02:09:05Z","timestamp":1580090945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Implementation of high\u2010resolution melting analysis of the porcupine (<i>PORCN)<\/i> gene for molecular diagnosis of focal dermal hypoplasia: Identification of a novel mutation"],"prefix":"10.1002","volume":"22","author":[{"given":"Mirna","family":"Mart\u00ednez\u2010Saucedo","sequence":"first","affiliation":[{"name":"Laboratory of Research in Genomics, Genetics and Bioinformatics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Ornelas\u2010Fuentes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Experimental Teratogenesis Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Dedden","sequence":"additional","affiliation":[{"name":"Laboratory of Research in Genomics, Genetics and Bioinformatics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"S\u00e1nchez\u2010Urbina","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Biology and Experimental Teratogenesis Hospital Infantil de M\u00e9xico Federico G\u00f3mez,  Mexico City M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor","family":"D\u00edaz\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Biology and Experimental Teratogenesis Hospital Infantil de M\u00e9xico Federico G\u00f3mez,  Mexico City M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-6695","authenticated-orcid":false,"given":"Guillermo","family":"Aquino\u2010Jarquin","sequence":"additional","affiliation":[{"name":"Laboratory of Research in Genomics, Genetics and Bioinformatics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Moreno\u2010Salgado","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Experimental Teratogenesis Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-654X","authenticated-orcid":false,"given":"Javier T.","family":"Granados\u2010Riveron","sequence":"additional","affiliation":[{"name":"Laboratory of Research in Genomics, Genetics and Bioinformatics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21505"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31473"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2012.06.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.04.029"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006437108"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222879"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.10"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0908s07"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0126-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.40"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10169"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1130"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.063438"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.088120"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.8.2766"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380060402"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380030202"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.87"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.068403"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.3165","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jgm.3165","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.3165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T14:59:42Z","timestamp":1694012382000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.3165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,16]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/jgm.3165"],"URL":"https:\/\/doi.org\/10.1002\/jgm.3165","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"type":"print","value":"1099-498X"},{"type":"electronic","value":"1521-2254"}],"subject":[],"published":{"date-parts":[[2020,2,16]]},"assertion":[{"value":"2019-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3165"}}