The spectrum of genetic variants and phenotypic features of Southeast Asian patients with Noonan syndrome. Issue 4 (19th February 2019)

• Record Type: Journal Article
• Authors: Koh, Ai‐Ling; Tan, Ee‐Shien; Brett, Maggie S.; Lai, Angeline H. M.; Jamuar, Saumya Shekhar; Ng, Ivy; Tan, Ene‐Choo
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 4(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-02-19
• Subjects: genetic testing -- molecular diagnosis -- Noonan syndrome -- RASopathies; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.581
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: 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. Methods: Patients were identified from the hospital's Genetics clinics after assessment by attending clinical geneticists. A targeted gene panel was used for next‐generation sequencing on genomic DNA extracted from the blood samples of 17 patients. Results: Heterozygous missense variants were identified in 13 patients: eight were in PTPN11, three in SOS1, and one each in RIT1 and KRAS . 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 PTPN11 variants had atrial septal defect. Only two had pulmonary stenosis which is reported to be common for PTPN11 mutation carriers. Another two had hypertrophic cardiomyopathy, a feature which is negatively associated with PTPN11 mutations. Conclusions: 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. Abstract : Heterozygous missense mutations in genes associated with Noonan syndrome were identified in 13 out of 17 patients from Southeast Asia. While the mutation spectrum in our patients appeared to be similar to populations elsewhere, the clinical manifestations seemed to be heterogeneous. Our patients with the same disease‐causing variant or affected gene did not have similar clinical presentations with each other or with what had been reported in other studies.