INTRODUCTION: Noonan syndrome (NS) is an autosomal-dominant disorder that presents with a characteristic face, short stature, skeletal anomalies, and congenital heart defects. Protein-tyrosine phosphatase nonreceptor-type 11 (PTPN11), encoding SHP-2, mutation was the first reported gene involved and accounted for 31% to 60% of cases of NS. The KRAS gene was the second reported gene and was recently identified in a small number of patients with NS.
OBJECTIVE: Our goal was to perform mutational analysis of PTPN11 and KRAS genes in children with NS.
METHODS: In this study we screened for mutation of the PTPN11 and KRAS genes in 73 Taiwanese patients with NS. The mutation analysis of the 15 coding exons and exon/intron boundaries was performed by polymerase chain reaction and direct sequencing of the PTPN11 gene. The mutation analysis of 5 coding exons and exon/intron boundaries was performed by polymerase chain reaction and direct sequencing of the KRAS gene. We identified 12 different missense PTPN11 mutations in 15 (21%) patients with NS and 2 different missense KRAS (V14I and I36M) mutations in 2 (3%) patients with NS. These PTPN11 gene mutations were clustered in exon 3 (n = 6) encoding the N-SH2 domain and 13 (n = 5) encoding the PTP domain.
CONCLUSIONS: This study provides support that PTPN11 and KRAS mutations are responsible for NS in Taiwanese patients.
Submitted by Fu-Sung Lo
- Copyright © 2008 by the American Academy of Pediatrics