THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROME
Objective: Dominant pathogenic variants in 29 RAS-MAPK (Rat-sarcoma-Mitogen-activated-protein-kinase) pathway genes, important for the regulation of cell growth, differentiation, aging and cell-cycle, are responsible for RASopathies, Noonan syndrome (NS) is the most common form. PTPN11 variants are...
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Istanbul University Press
2021-01-01
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| Series: | İstanbul Tıp Fakültesi Dergisi |
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| author | Güven Toksoy Fatih Tepgeç Tuğba Saraç Sivrikoz İbrahim Halil Kalelioğlu Selma Demir Recep Has Atıl Yüksel Zehra Oya Uyguner Seher Başaran |
| author_facet | Güven Toksoy Fatih Tepgeç Tuğba Saraç Sivrikoz İbrahim Halil Kalelioğlu Selma Demir Recep Has Atıl Yüksel Zehra Oya Uyguner Seher Başaran |
| author_sort | Güven Toksoy |
| collection | DOAJ |
| description | Objective: Dominant pathogenic variants in 29 RAS-MAPK (Rat-sarcoma-Mitogen-activated-protein-kinase) pathway genes, important for the regulation of cell growth, differentiation, aging and cell-cycle, are responsible for RASopathies, Noonan syndrome (NS) is the most common form. PTPN11 variants are detected in 50% of the cases, 90% being identified in the first SH2 and in the catalytic domain at the N- and C-terminals of the peptide, respectively. Increased nuchal translucency (NT), lymphatic system anomalies (cystic hygroma, pleural effusion, ascites), cardiac anomalies, polyhydramnios, short limb and macrocephaly are the NS-associated prenatal findings. PTPN11 association is reported in 2-3% of normal karyotyped fetuses with NT and in >10% when other NS findings are included. Material and Method: PTPN11 analysis with different approaches in 246 normal karyotyped prenatal cases with NS-associated USG findings were retrospectively evaluated. The targeted PTPN11 regions in 200 and the whole gene structure of 46 cases were examined by Sanger sequencing. Results: Pathogenic variants, including two novel variants (p.P107S and p.M504T), were identified in two fetuses with isolated NT and in three fetuses with multiple USG findings, leading to a 2% of detection rate, all found in targeted exons. Two of six cases, further investigated for targets of four Rasopathy genes, had causative genes in SOS1. One of three terminated fetuses, investigated for the targeted-gene panel, had a causative gene in RAF1 genes. Both the isolated NT and multiple USG finding groups revealed an equal detection rate of 2.3%. Discussion: PTPN11 is responsible for 50% of RASopathies and 90% of the pathogenic variants are delineated in the targeted exons. The rational, cost-effective approach for the clarification of the genetic basis of RASopathies is screening the addressed exons of PTPN11 followed by the other exons and other RASopathy related genes. |
| format | Article |
| id | doaj-art-daa587c3a7ef47b9a425b04c93a35e7e |
| institution | Kabale University |
| issn | 1305-6441 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Istanbul University Press |
| record_format | Article |
| series | İstanbul Tıp Fakültesi Dergisi |
| spelling | doaj-art-daa587c3a7ef47b9a425b04c93a35e7e2025-08-20T03:53:18ZengIstanbul University Pressİstanbul Tıp Fakültesi Dergisi1305-64412021-01-01841343910.26650/IUITFD.2020.803356123456THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROMEGüven Toksoy0https://orcid.org/0000-0002-8103-9980Fatih Tepgeç1https://orcid.org/0000-0001-8413-6949Tuğba Saraç Sivrikoz2https://orcid.org/0000-0001-5482-9429İbrahim Halil Kalelioğlu3https://orcid.org/0000-0002-5504-2166Selma Demir4https://orcid.org/0000-0002-0964-5513Recep Has5https://orcid.org/0000-0002-1372-8506Atıl Yüksel6https://orcid.org/0000-0002-6487-0860Zehra Oya Uyguner7https://orcid.org/0000-0002-2035-4338Seher Başaran8https://orcid.org/0000-0001-8668-4746İstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, TürkiyeTrakya Üniversitesi, Edirne, Turkiyeİstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, TürkiyeObjective: Dominant pathogenic variants in 29 RAS-MAPK (Rat-sarcoma-Mitogen-activated-protein-kinase) pathway genes, important for the regulation of cell growth, differentiation, aging and cell-cycle, are responsible for RASopathies, Noonan syndrome (NS) is the most common form. PTPN11 variants are detected in 50% of the cases, 90% being identified in the first SH2 and in the catalytic domain at the N- and C-terminals of the peptide, respectively. Increased nuchal translucency (NT), lymphatic system anomalies (cystic hygroma, pleural effusion, ascites), cardiac anomalies, polyhydramnios, short limb and macrocephaly are the NS-associated prenatal findings. PTPN11 association is reported in 2-3% of normal karyotyped fetuses with NT and in >10% when other NS findings are included. Material and Method: PTPN11 analysis with different approaches in 246 normal karyotyped prenatal cases with NS-associated USG findings were retrospectively evaluated. The targeted PTPN11 regions in 200 and the whole gene structure of 46 cases were examined by Sanger sequencing. Results: Pathogenic variants, including two novel variants (p.P107S and p.M504T), were identified in two fetuses with isolated NT and in three fetuses with multiple USG findings, leading to a 2% of detection rate, all found in targeted exons. Two of six cases, further investigated for targets of four Rasopathy genes, had causative genes in SOS1. One of three terminated fetuses, investigated for the targeted-gene panel, had a causative gene in RAF1 genes. Both the isolated NT and multiple USG finding groups revealed an equal detection rate of 2.3%. Discussion: PTPN11 is responsible for 50% of RASopathies and 90% of the pathogenic variants are delineated in the targeted exons. The rational, cost-effective approach for the clarification of the genetic basis of RASopathies is screening the addressed exons of PTPN11 followed by the other exons and other RASopathy related genes.https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/E893A966FC784DC2A45B3A4D6C2506F8ptpn11noonan syndromeincreased nuchal translucencycystic hygromapleural effusion |
| spellingShingle | Güven Toksoy Fatih Tepgeç Tuğba Saraç Sivrikoz İbrahim Halil Kalelioğlu Selma Demir Recep Has Atıl Yüksel Zehra Oya Uyguner Seher Başaran THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROME İstanbul Tıp Fakültesi Dergisi ptpn11 noonan syndrome increased nuchal translucency cystic hygroma pleural effusion |
| title | THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROME |
| title_full | THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROME |
| title_fullStr | THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROME |
| title_full_unstemmed | THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROME |
| title_short | THE EFFECTIVENESS OF PTPN11 GENE ANALYSIS IN THE PRENATAL DIAGNOSIS OF NOONAN SYNDROME |
| title_sort | effectiveness of ptpn11 gene analysis in the prenatal diagnosis of noonan syndrome |
| topic | ptpn11 noonan syndrome increased nuchal translucency cystic hygroma pleural effusion |
| url | https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/E893A966FC784DC2A45B3A4D6C2506F8 |
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