{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:31:47Z","timestamp":1788269507355,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:00:00Z","timestamp":1569542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypotrichosis with juvenile macular dystrophy (HJMD) is an autosomal recessive disorder characterized by abnormal growth of scalp hair and juvenile\u00a0macular degeneration leading to blindness. We have explored the genetic basis of HJMD in a large consanguineous family with 12 affected patients, 1\u201376\u00a0years of age, with characteristic phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We first applied genome\u2010wide homozygosity mapping to 10 affected individuals for linkage analysis to identify the genomic region of the defective gene. All affected individuals shared a 7.2\u00a0Mb region of homozygosity on chromosome 16q21\u201022.3, which harbored 298 genes, including <jats:italic>CDH3<\/jats:italic>, previously associated with HJMD. However, whole\u2010exome sequencing (WES) failed to identify the causative mutation in <jats:italic>CDH3<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Further investigation revealed a missense variant in a gene\u00a0closely linked to <jats:italic>CDH3<\/jats:italic> (1.4\u00a0Mb distance: <jats:italic>FHOD1<\/jats:italic>: c.1306A&gt;G, p.Arg436Gly). This variant was homozygous in all affected individuals and heterozygous in 18 out of 19 obligate carriers. While this variant was found by bioinformatics predictions to be likely pathogenic, a knock\u2010in mouse for this variant, made by the CRISPR\/Cas, showed no disease phenotype. However, using whole\u2010genome sequencing (WGS), we were able to identify a novel <jats:italic>Alu<\/jats:italic> recombination\u2010mediated deletion in <jats:italic>CDH3<\/jats:italic>:c.del161\u2010811_246\u00a0+\u00a01,044.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>WGS was able to identify a deep intronic deletion mutation, not detected by WES.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.975","type":"journal-article","created":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T03:06:41Z","timestamp":1569640001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hypotrichosis with juvenile macular dystrophy: Combination of whole\u2010genome sequencing and genome\u2010wide homozygosity mapping identifies a large deletion in <i>CDH3<\/i> initially undetected by whole\u2010exome sequencing\u2014A lesson from next\u2010generation sequencing"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3512-0654","authenticated-orcid":false,"given":"Amir Hossein","family":"Saeidian","sequence":"first","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, and Jefferson Institute of Molecular Medicine Thomas Jefferson University Philadelphia PA USA"},{"name":"Genetics, Genomics and Cancer Biology Ph.D. Program Thomas Jefferson University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4298-9147","authenticated-orcid":false,"given":"Hassan","family":"Vahidnezhad","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, and Jefferson Institute of Molecular Medicine Thomas Jefferson University Philadelphia PA USA"},{"name":"Biotechnology Research Center Department of Molecular Medicine Pasteur Institute of Iran Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4253-6503","authenticated-orcid":false,"given":"Leila","family":"Youssefian","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, and Jefferson Institute of Molecular Medicine Thomas Jefferson University Philadelphia PA USA"},{"name":"Genetics, Genomics and Cancer Biology Ph.D. Program Thomas Jefferson University Philadelphia PA USA"},{"name":"Department of Medical Genetics School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheila","family":"Sotudeh","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Children's Medical Center Pediatric Center of Excellence Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meisam","family":"Sargazi","sequence":"additional","affiliation":[{"name":"Alzahra Eye Hospital Research Center Zahedan University of Medical Sciences Zahedan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirous","family":"Zeinali","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center Department of Molecular Medicine Pasteur Institute of Iran Tehran Iran"},{"name":"Kawsar Human Genetics Research Center Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-807X","authenticated-orcid":false,"given":"Jouni","family":"Uitto","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology, and Jefferson Institute of Molecular Medicine Thomas Jefferson University Philadelphia PA 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