PTPN11 gen mutasyonlarının noonan sendromlu hastalarda taranması
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Date
2006
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Biyoteknoloji Enstitüsü
Abstract
Noonan syndrome (NS) is an autosomal dominant disorder characterized by distinctive facial features, short stature, congenital heart disease, cryptorchidism, and lymphatic dysplasia. This syndrome is estimated to be seen in 1/1500-1/2500 live births. Mutations in the PTPN11 gene are detected in nearly 50% of affected individuals. The PTPN11 gene encodes for a nonreceptor protein tyrosine phosphatase, SHP-2, which contains N-SH2 and C-SH2 domains in the amino terminal and a PTP domain in the carboxy terminal. PTPN11 missense mutations cluster in the N-SH2 and PTP domains, which are involved in switching the protein between its inactive and active conformations. In this study, 20 patients, clinically diagnosed with NS, were screened for mutations in 8 exons of the PTPN11 gene. These exons were screened with PCR-SSCP, PCR-DHPLC, and PCR-DNA sequence analysis protocols. Mutation analysis revealed the p.Asn308Asp alteration in three patients in exon 8, p.Ala72Ser alteration in a patient in exon 3, p.Tyr63Cys alteration in a patient in exon3, and p.Asn58Asp alteration in a patient in exon 3. All mutations were detected with DHPLC. However, only p.Tyr63Cys and p.Ala72Ser mutations were found with SSCP. The p.Asn308Asp mutation was confirmed with a PCR-RFLP protocol. Our results show that it will be practical to first screen exons 3 and 8 of PTPN11 with PCRDHPLC in patients with NS. Key Words: DHPLC, DNA sequence analysis, Noonan syndrome, PTPN11, PCR, SSCP
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Biyoteknoloji