{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T19:40:55Z","timestamp":1772566855653,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["107-2314-B-371-009-MY3"],"award-info":[{"award-number":["107-2314-B-371-009-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007632","name":"Changhua Christian Hospital","doi-asserted-by":"publisher","award":["108-CCH-IRP-101"],"award-info":[{"award-number":["108-CCH-IRP-101"]}],"id":[{"id":"10.13039\/501100007632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Skeletal dysplasia (SD) is a complex group of bone and cartilage disorders often detectable by fetal ultrasound, but the definitive diagnosis remains challenging because the phenotypes are highly variable and often overlap among different disorders. The molecular mechanisms underlying this condition are also diverse. Hundreds of genes are involved in the pathogenesis of SD, but most of them are yet to be elucidated, rendering genotyping almost infeasible except those most common such as fibroblast growth factor receptor 3 (FGFR3), collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), diastrophic dysplasia sulfate transporter (DTDST), and SRY-box 9 (SOX9). Here, we report the use of trio-based whole exome sequencing (trio-WES) with comprehensive gene set analysis in two Taiwanese non-consanguineous families with fetal SD at autopsy. A biparental-origin homozygous c.509G&gt;A(p.G170D) mutation in peptidylprolyl isomerase B (PPIB) gene was identified. The results support a diagnosis of a rare form of autosomal recessive SD, osteogenesis imperfecta type IX (OI IX), and confirm that the use of a trio-WES study is helpful to uncover a genetic explanation for observed fetal anomalies (e.g., SD), especially in cases suggesting autosomal recessive inheritance. Moreover, the finding of an identical PPIB mutation in two non-consanguineous families highlights the possibility of the founder effect, which deserves future investigations in the Taiwanese population.<\/jats:p>","DOI":"10.3390\/diagnostics10050286","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T03:45:20Z","timestamp":1588909520000},"page":"286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Whole Exome Sequencing with Comprehensive Gene Set Analysis Identified a Biparental-Origin Homozygous c.509G&gt;A Mutation in PPIB Gene Clustered in Two Taiwanese Families Exhibiting Fetal Skeletal Dysplasia during Prenatal Ultrasound"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-2757","authenticated-orcid":false,"given":"Ting-Yu","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan"},{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan 32023, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Fang","family":"Chung","sequence":"additional","affiliation":[{"name":"Institute of Biomedical informatics, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Ju","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Ph.D. programs in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Ping","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hsiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman A.","family":"Ginsberg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University Medical Center, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwo-Chin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan"},{"name":"Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan 32023, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-2917","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Department of Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan"},{"name":"Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 10041, Taiwan"},{"name":"Department of Biomedical Science, Dayeh University, Changhua 51591, Taiwan"},{"name":"Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00247-016-3725-5","article-title":"Evaluating skeletal dysplasias on prenatal ultrasound: An emphasis on predicting lethality","volume":"47","author":"Milks","year":"2017","journal-title":"Pediatr Radiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1196\/annals.1402.072","article-title":"The skeletal dysplasias: Clinical-molecular correlations","volume":"1117","author":"Rimoin","year":"2007","journal-title":"Ann. 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