{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T04:24:40Z","timestamp":1782879880475,"version":"3.54.5"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI143810"],"award-info":[{"award-number":["R01 AI143810"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011960","name":"DEBRA International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011960","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Among the approximately 8000 Mendelian disorders, &amp;gt;1000 have cutaneous manifestations. In many of these conditions, the underlying mutated genes have been identified by DNA-based techniques which, however, can overlook certain types of mutations, such as exonic-synonymous and deep-intronic sequence variants. Whole-transcriptome sequencing by RNA sequencing (RNA-seq) can identify such mutations and provide information about their consequences.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We analyzed the whole transcriptome of 40 families with different types of Mendelian skin disorders with extensive genetic heterogeneity. The RNA-seq data were examined for variant detection and prioritization, pathogenicity confirmation, RNA expression profiling, and genome-wide homozygosity mapping in the case of consanguineous families. Among the families examined, RNA-seq was able to provide information complementary to DNA-based analyses for exonic and intronic sequence variants with aberrant splicing. In addition, we tested the possibility of using RNA-seq as the first-tier strategy for unbiased genome-wide mutation screening without information from DNA analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found pathogenic mutations in 35 families (88%) with RNA-seq in combination with other next-generation sequencing methods, and we successfully prioritized variants and found the culprit genes. In addition, as a novel concept, we propose a pipeline that increases the yield of variant calling from RNA-seq by concurrent use of genome and transcriptome references in parallel.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results suggest that \u201cclinical RNA-seq\u201d could serve as a primary approach for mutation detection in inherited diseases, particularly in consanguineous families, provided that tissues and cells expressing the relevant genes are available for analysis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvab042","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T20:10:51Z","timestamp":1615320651000},"page":"876-888","source":"Crossref","is-referenced-by-count":27,"title":["Whole-Transcriptome Analysis by RNA Sequencing for Genetic Diagnosis of Mendelian Skin Disorders in the Context of Consanguinity"],"prefix":"10.1093","volume":"67","author":[{"given":"Leila","family":"Youssefian","sequence":"first","affiliation":[{"name":"Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA"},{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA"},{"name":"Genetics, Genomics and Cancer Biology PhD Program, Thomas Jefferson University, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Hossein","family":"Saeidian","sequence":"additional","affiliation":[{"name":"Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA"},{"name":"Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA"},{"name":"Genetics, Genomics and Cancer Biology PhD Program, Thomas Jefferson University, Philadelphia, PA, 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