Te frst PTPN11 mutations in hotspot exons reported in Moroccan children with Noonan syndrome and comparison of mutation rate to previous studies

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 beencarried out in diferent populations. Tus, the aim of this study was to screen, for the frst time, PTPN11 mutations in a series ofMoroccan Noonan syndrome patients.Materials and methods: We used bidirectional sequencing of exons 3 and 8, considered as PTPN11 mutation hot spots, and thencompared the rate of mutational events of these exons between diferent 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%).Te rate of mutation in our cohort did not difer from that of other populations. However, we found signifcant diferences in themutation rate of exon 8 between one Japanese cohort and some populations, which requires more investigations to be explained.Conclusion: Te present study allowed identifcation of mutations clustered in exons 3 and 8 of the PTPN11 gene in a MoroccanNoonan syndrome cohort and enabled us to give appropriate genetic counseling to the mutation-positive patients.