{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:51:03Z","timestamp":1762005063736,"version":"3.41.2"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T00:00:00Z","timestamp":1550534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/CG\/006\/2013","NMRC\/CG\/M003\/2017"],"award-info":[{"award-number":["NMRC\/CG\/006\/2013","NMRC\/CG\/M003\/2017"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Noonan syndrome (NS) is an autosomal dominant disorder that belongs to a group of developmental disorders called RASopathies with overlapping features and multiple causative genes. The aim of the study was to identify mutations underlying this disorder in patients from Southeast Asia and characterize their clinical presentations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were identified from the hospital's Genetics clinics after assessment by attending clinical geneticists. A targeted gene panel was used for next\u2010generation sequencing on genomic DNA extracted from the blood samples of 17 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Heterozygous missense variants were identified in 13 patients: eight were in <jats:italic>PTPN11<\/jats:italic>, three in <jats:italic>SOS1<\/jats:italic>, and one each in <jats:italic>RIT1<\/jats:italic> and <jats:italic>KRAS<\/jats:italic>. All are known variants that have been reported in patients with NS. Of the 13 patients with identified variants, 10 had short stature, the most common feature for NS. Four of the eight patients with <jats:italic>PTPN11<\/jats:italic> variants had atrial septal defect. Only two had pulmonary stenosis which is reported to be common for <jats:italic>PTPN11<\/jats:italic> mutation carriers. Another two had hypertrophic cardiomyopathy, a feature which is negatively associated with <jats:italic>PTPN11 <\/jats:italic>mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study provides the mutation and phenotypic spectrum of NS from a new population group. The molecular testing yield of 76% is similar to other studies and shows that the targeted panel approach is useful for identifying genetic mutations in NS which has multiple causative genes. The molecular basis for the phenotypes of the remaining patients remains unknown and would need to be uncovered via sequencing of additional genes or other investigative methods.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.581","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T07:37:51Z","timestamp":1550648271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The spectrum of genetic variants and phenotypic features of Southeast Asian patients with Noonan syndrome"],"prefix":"10.1002","volume":"7","author":[{"given":"Ai\u2010Ling","family":"Koh","sequence":"first","affiliation":[{"name":"Department of Paediatrics KK Women's &amp; Children's Hospital Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ee\u2010Shien","family":"Tan","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Paediatrics KK Women's &amp; Children's Hospital Singapore"},{"name":"Paediatrics Academic Clinical Programme SingHealth Duke\u2010NUS Graduate Medical School  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie S.","family":"Brett","sequence":"additional","affiliation":[{"name":"Research Laboratory KK Women's &amp; Children's Hospital Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angeline H. 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