{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:52:35Z","timestamp":1792619555667,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rare diseases are complex disorders with huge variability in clinical manifestations. Decreasing cost of next\u2010generation sequencing (NGS) tests in recent years made it affordable. We witnessed the diagnostic yield and clinical use of different NGS strategies on a myriad of monogenic disorders in a pediatric setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Next\u2010generation sequencing tests are performed for 98 unrelated Chinese patients within their first year of life, who were admitted to Xin Hua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, during a 2\u2010year period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical indications for NGS tests included a range of medical concerns. The mean age was 4.4\u00a0\u00b1\u00a04.2\u00a0months of age for infants undergoing targeting specific (known) disease\u2010causing genes (TRS) analysis, and 4.4\u00a0\u00b1\u00a04.3\u00a0months of age for whole\u2010exome sequencing (WES) (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&gt;\u00a00.05). A molecular diagnosis is done in 72 infants (73.47%), which finds a relatively high yield with phenotypes of metabolism\/homeostasis abnormality (HP: 0001939) (odds ratio, 1.83; 95% CI, 0.56\u20136.04;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.32) and a significantly low yield with atypical symptoms (without a definite HPO term) (odds ratio, 0.08; 95% CI, 0.01\u20130.73;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.03). TRS analysis provides molecular yields higher than WES (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.01). Ninety\u2010eight different mutations are discovered in 72 patients. Twenty\u2010seven of them have not been reported previously. Nearly half (43.06%, 31\/72) of the patients are found to carry 11 common disorders, mostly being inborn errors of metabolism (IEM) and neurogenetic disorders and all of them are observed through TRS analysis. Eight positive cases are identified through WES, and all of them are sporadic, of highly variable phenotypes and severity. There are 26 patients with negative findings in this study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides evidence that NGS can yield high success rates in a tertiary pediatric setting, but suggests that the scope of known Mendelian conditions may be considerably broader than currently recognized.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.684","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T21:25:38Z","timestamp":1554845138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clinical utility in infants with suspected monogenic conditions through next\u2010generation sequencing"],"prefix":"10.1002","volume":"7","author":[{"given":"Sha","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Neonatal Medicine Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Genetic Metabolism Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-213X","authenticated-orcid":false,"given":"Tianwen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine Xin\u2010Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0474-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2196\/ijmr.7352"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2016.1222906"},{"issue":"6","key":"e_1_2_8_5_1","first-page":"359","article-title":"Rare diseases in Europe: From a wide to a local perspective","volume":"18","author":"Baldovino S.","year":"2016","journal-title":"Israel Medical Association 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