{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:28:43Z","timestamp":1787318923867,"version":"build-2736575974"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T00:00:00Z","timestamp":1632096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Nagashima-type palmoplantar keratoderma (NPPK) is characterized by non-progressive, diffuse, and cross-gradient hyperkeratosis caused by mutations in the\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    gene on chromosome 18q21.33. Chromosome 18q deletion syndrome (18q- syndrome) is a terminal deletion or microdeletion syndrome characterized by intellectual disability and congenital malformations. This paper describes an 18-year-old man with palmoplantar keratoderma and diffuse white matter abnormalities in the brain. Trio-based exome sequencing (ES) revealed a suspected mosaic compound heterozygous mutation for c.796C&amp;gt;T (p.Arg266\n                    <jats:sup>\u2217<\/jats:sup>\n                    ) in exon 8 inherited from the mother and a\n                    <jats:italic>de novo<\/jats:italic>\n                    exons 4\u20136 deletion of\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    . Additional copy number variant (CNV) analysis of the ES data indicated a heterozygous gross deletion of 18q22.3-q23. The two\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    gene variants were verified by Sanger sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Finally, low-coverage whole-genome sequencing (WGS) confirmed the 18q22.3-q23 deletion and additionally detected a mosaic 18q21.33-q22.3 deletion, together explaining NPPK and the neurological phenotypes of the proband. The gross deletion of all exons of\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    was revealed for the first time. More rarely, c.796C&amp;gt;T (p.Arg266\n                    <jats:sup>\u2217<\/jats:sup>\n                    ) was likely to be mosaic, while the exon deletion was mosaic. In conclusion, the combination of multiple molecular genetic testing methods provides comprehensive informative molecular findings and promotes the diagnosis of complex diseases, as in this case.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2021.707411","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T02:25:13Z","timestamp":1632104713000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of a Rare Case With Nagashima-Type Palmoplantar Keratoderma and 18q Deletion Syndrome via Exome Sequencing and Low-Coverage Whole-Genome Sequencing"],"prefix":"10.3389","volume":"12","author":[{"given":"Qianqian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00420","article-title":"Exome sequencing diagnoses X-linked moesin-associated immunodeficiency in a primary immunodeficiency case.","volume":"9","author":"Bradshaw","year":"2018","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/nature08516","article-title":"Origins and functional impact of copy number variation in the human genome.","volume":"464","author":"Conrad","year":"2010","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.ajhg.2011.11.008","article-title":"Disruption of teashirt zinc finger homeobox 1 is associated with congenital aural atresia in humans.","volume":"89","author":"Feenstra","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1136\/jmg.6.4.388","article-title":"Immunological profile in a chromosome 18 deletion syndrome with IgA deficiency.","volume":"6","author":"Finley","year":"1969","journal-title":"J. Med. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.ajhg.2012.08.005","article-title":"Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth.","volume":"91","author":"Fromer","year":"2012","journal-title":"J. Hum. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.jaad.2019.11.004","article-title":"Nagashima-type palmoplantar keratosis in Finland caused by a SERPINB7 founder mutation.","volume":"83","author":"Hannula-Jouppi","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"B7","doi-asserted-by":"crossref","first-page":"D1018","DOI":"10.1093\/nar\/gky1105","article-title":"Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.","volume":"47","author":"Kohler","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1038\/jid.2014.156","article-title":"Nagashima-type palmoplantar keratosis: a common Asian type caused by SERPINB7 protease inhibitor deficiency.","volume":"134","author":"Kubo","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.ajhg.2013.09.015","article-title":"Mutations in SERPINB7, encoding a member of the serine protease inhibitor superfamily, cause Nagashima-type palmoplantar keratosis.","volume":"93","author":"Kubo","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1002\/ajmg.a.31072","article-title":"18q deletions: clinical, molecular, and brain MRI findings of 14 individuals.","volume":"140","author":"Linnankivi","year":"2006","journal-title":"Am. J. Med. Genet. A"},{"key":"B11","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1002\/jmri.10383","article-title":"18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images.","volume":"18","author":"Linnankivi","year":"2003","journal-title":"J. Magn. Reson. Imaging"},{"key":"B12","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/humu.20206","article-title":"Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6.","volume":"26","author":"Miksch","year":"2005","journal-title":"Hum Mutat."},{"key":"B13","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.ymgme.2011.01.002","article-title":"Novel splice site mutations and a large deletion in three patients with the cblF inborn error of vitamin B12 metabolism.","volume":"102","author":"Miousse","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"B14","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1001\/jama.2015.10078","article-title":"Molecular diagnostic yield of chromosomal microarray analysis and whole-exome sequencing in children with autism spectrum disorder.","volume":"314","author":"Tammimies","year":"2015","journal-title":"JAMA"},{"key":"B16","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1002\/ajmg.a.30916","article-title":"Absent pulmonary valve with intact ventricular septum and patent ductus arteriosus: a specific cardiac phenotype associated with deletion 18q syndrome.","volume":"138","author":"Versacci","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"B17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ajog.2018.05.030","article-title":"Prospective chromosome analysis of 3429 amniocentesis samples in China using copy number variation sequencing.","volume":"219","author":"Wang","year":"2018","journal-title":"Am. J. Obstet. Gynecol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.707411\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T02:25:21Z","timestamp":1632104721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.707411\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,20]]},"references-count":17,"alternative-id":["10.3389\/fgene.2021.707411"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.707411","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,20]]},"article-number":"707411"}}