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Mutation N308T of protein tyrosine phosphatase SHP-2 in two Senegalese patients with Noonan syndrome


Affiliations
1 Laboratoire de Cytologie Clinique, Cytogénétique et Biologie de la Reproduction et du Développement, CHU Le Dantec, Dakar, Senegal
2 Service de Cardiologie, CHUN de Fann, Dakar, Senegal
3 Laboratoire d’Immunologie, FMPO, UCAD, Dakar, Senegal
4 Laboratoire de Cytologie Clinique, Cytogénétique et Biologie de la Reproduction et du Développement, CHU Le Dantec, Dakar, Senegal
5 Hôpital d’Enfants Albert Royer, CHUN de Fann, Dakar, Senegal
 

Noonan syndrome is a genetic autosomal dominant disorder characterized by facial dysmorphy, short stature, delayed puberty and congenital heart defects. The first gene implicated in this syndrome is PTPN11, encoding protein tyrosine phosphatase SHP-2. Several studies worldwide have identified missense mutations in this gene in patients with Noonan syndrome. Our objective focused on mutations screening of PTPN11 on a Senegalese population with Noonan syndrome. Six patients clinically diagnosed with Noonan syndrome were included in this study. DNA was extracted from whole blood by phenol chloroform. Mutation screening was performed by bidirectional sequencing of amplified polymerase chain reaction (PCR) products of PTPN11 exons frequently mutated in Noonan syndrome. This study identified in two patients, a c.923A>C mutation in exon 8, predicting Asn308Thr (N308T) on SHP-2 protein. This is the first time that this mutation is described in Noonan syndrome in Africa, while codon 308 was reported as a hot spot mutation site in other populations. Frequently reported amino acid substitutions were Asn308Asp and Asn308Ser. All these mutations affected the protein tyrosine phosphatase domain (PTP) of SHP-2 protein exerting a gain of function which would likely explain observed phenotypes in patients.

Keywords

Mutation, N308T, Protein Tyrosine Phosphatise (PTP), SHP-2 Protein, Noonan Syndrome, Senegal.
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  • Mutation N308T of protein tyrosine phosphatase SHP-2 in two Senegalese patients with Noonan syndrome

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Authors

Rokhaya Ndiaye
Laboratoire de Cytologie Clinique, Cytogénétique et Biologie de la Reproduction et du Développement, CHU Le Dantec, Dakar, Senegal
Coumba Ndiaye
Laboratoire de Cytologie Clinique, Cytogénétique et Biologie de la Reproduction et du Développement, CHU Le Dantec, Dakar, Senegal
Mohamed Leye
Service de Cardiologie, CHUN de Fann, Dakar, Senegal
Babacar Mbengue
Laboratoire d’Immunologie, FMPO, UCAD, Dakar, Senegal
Mama Sy Diallo
Laboratoire de Cytologie Clinique, Cytogénétique et Biologie de la Reproduction et du Développement, CHU Le Dantec, Dakar, Senegal
Jean Pascal Demba Diop
Laboratoire de Cytologie Clinique, Cytogénétique et Biologie de la Reproduction et du Développement, CHU Le Dantec, Dakar, Senegal
Omar Faye
Laboratoire de Cytologie Clinique, Cytogénétique et Biologie de la Reproduction et du Développement, CHU Le Dantec, Dakar, Senegal
Ibrahima Bara Diop
Service de Cardiologie, CHUN de Fann, Dakar, Senegal
Haby Signate Sy
Hôpital d’Enfants Albert Royer, CHUN de Fann, Dakar, Senegal

Abstract


Noonan syndrome is a genetic autosomal dominant disorder characterized by facial dysmorphy, short stature, delayed puberty and congenital heart defects. The first gene implicated in this syndrome is PTPN11, encoding protein tyrosine phosphatase SHP-2. Several studies worldwide have identified missense mutations in this gene in patients with Noonan syndrome. Our objective focused on mutations screening of PTPN11 on a Senegalese population with Noonan syndrome. Six patients clinically diagnosed with Noonan syndrome were included in this study. DNA was extracted from whole blood by phenol chloroform. Mutation screening was performed by bidirectional sequencing of amplified polymerase chain reaction (PCR) products of PTPN11 exons frequently mutated in Noonan syndrome. This study identified in two patients, a c.923A>C mutation in exon 8, predicting Asn308Thr (N308T) on SHP-2 protein. This is the first time that this mutation is described in Noonan syndrome in Africa, while codon 308 was reported as a hot spot mutation site in other populations. Frequently reported amino acid substitutions were Asn308Asp and Asn308Ser. All these mutations affected the protein tyrosine phosphatase domain (PTP) of SHP-2 protein exerting a gain of function which would likely explain observed phenotypes in patients.

Keywords


Mutation, N308T, Protein Tyrosine Phosphatise (PTP), SHP-2 Protein, Noonan Syndrome, Senegal.