Title : High frequency of hot-spot mutation in PTPN11 gene among Moroccan patients with Noonan Syndrome
Abstract:
Background: Noonan syndrome (NS; OMIM 163950) is an autosomal dominant Rasopathy with variable clinical expression and genetic heterogeneity. Clinical manifestations include characteristic facial features, short stature, and cardiac anomalies. Mutations in protein-tyrosine phosphatase, non-receptor-type 11 (PTPN11), encoding SHP-2, account for about half of NS patients, SOS1 in approximately 13%, RAF1 and RIT1 each in 5%, and KRAS in fewer than 5%. Other genes have been reported to cause NS in less than 1% of cases including NRAS, BRAF, and MAP2K1. Several additional genes associated with a Noonan-syndrome-like phenotype have been identified.
Methods: We report molecular analysis of 41 patients with NS phenotype belonging to 39 families. We screened for hot-spot mutations (exons 3, 8 and 13) in PTPN11 gene by Sanger sequencing.
Results: Twenty patients were carrying heterozygous mutation of PTPN11 gene with a higher frequency (48%) compared to the literature.
Conclusion: Our findings expand the mutation spectrum of Moroccan patients with NS phenotype in whom the analysis of hot-spot mutations showed a high frequency of exons 3 and 8. This screening test allowed us to establish a molecular diagnosis in almost half of the patients with a good benefit-cost ratio, with an appropriate management and a genetic counseling.
Key words: Noonan syndrome, high hot-spot frequency, PTPN11 gene.
