The first PTPN11 mutations in hotspot exons reported in Moroccan children with Noonan syndrome and comparison of mutation rate to the previous studies

Authors: IHSSANE EL BOUCHIKHI, IMANE SAMRI, MOHAMMED IRAQUI HOUSSAINI, SAAID TRHANINT, LAILA BOUGUENOUCH, HANANE SAYEL, MOUSTAPHA HIDA, SAMIR ATMANI, KARIM OULDIM

Abstract: Background/aim: Noonan syndrome is an autosomal dominant disorder with an incidence of 1/1000?2500. It results from protein-tyrosine phosphatase, nonreceptor type 11 (PTPN11) mutations in roughly 50% of cases. Mutational screening of PTPN11 has been carried out in different populations. Thus, the aim of this study was to screen, for the first time, PTPN11 mutations in a series of Moroccan Noonan syndrome patients. Materials and methods: We used bidirectional sequencing of exons 3 and 8, considered as PTPN11 mutation hot spots, and then compared the rate of mutational events of these exons between different populations using chi-square and Fisher?s exact tests. Results: We detected 3 heterozygous mutations (Asp61Gly, Tyr63Cys, and Asn308Ser) in 4 individuals of 16 sporadic patients (25%). The rate of mutation in our cohort did not differ from that of other populations. However, we found significant differences in the mutation rate of exon 8 between one Japanese cohort and some populations, which requires more investigations to be explained. Conclusion: The present study allowed identification of mutations clustered in exons 3 and 8 of the PTPN11 gene in a Moroccan Noonan syndrome cohort and enabled us to give appropriate genetic counseling to the mutation-positive patients.

Keywords: Noonan syndrome, PTPN11, mutation analysis, SHP-2, mutation rate comparison

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