title: The first PTPN1 1 mutations in hotspot exons reported in Moroccan children with Noonan syndrome and comparison of mutation rate to previous studies.
abstract: OBJECTIVE
  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.
  
  
  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 (Asp6lGly, 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Ihssane
authors.initials: I
authors.lastname: El Bouchikhi
authors.forename: Imane
authors.initials: I
authors.lastname: Samri
authors.forename: Mohammed
authors.initials: M
authors.lastname: Iraqui Houssaini
authors.forename: Saaid
authors.initials: S
authors.lastname: Trhanint
authors.forename: Laila
authors.initials: L
authors.lastname: Bouguenouch
authors.forename: Hanane
authors.initials: H
authors.lastname: Sayel
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hida
authors.forename: Samir
authors.initials: S
authors.lastname: Atmani
authors.forename: Karim
authors.initials: K
authors.lastname: Ouldim
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D009018:Morocco; D009154:Mutation; D059645:Mutation Rate; D009634:Noonan Syndrome / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*
chemical_list: D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11