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A novel PTPN11 mutation in LEOPARD syndrome
E Conti1, T Dottorini, A Sarkozy
1Ospedale CSS, IRCCS, San Giovanni Rotondo, Italy.
Human Mutation
|February 13, 2004
Summary
Noonan syndrome (NS) and LEOPARD syndrome (LS) share PTPN11 gene mutations. A new PTPN11 mutation, Gln506Pro, identified in an LS patient, highlights the need for broader genetic screening in rare cases.
Area of Science:
- Genetics
- Molecular Biology
- Biochemistry
Background:
- Noonan syndrome (NS) and LEOPARD syndrome (LS) are genetic disorders associated with mutations in the PTPN11 gene.
- Previously, only two recurrent PTPN11 mutations (Tyr279Cys and Thr468Met) were identified in LS patients.
Observation:
- This study reports a novel PTPN11 mutation, c.1517A>C, resulting in a glutamine to proline substitution at amino acid 506 (Gln506Pro) in the SHP2 phosphatase domain.
- This mutation occurred in a single patient diagnosed with LEOPARD syndrome.
Findings:
- The Gln506Pro mutation is located in a known mutation hotspot within the PTPN11 phosphatase domain.
- Molecular modeling predicts that Gln506Pro disrupts inter-domain contacts, leading to enhanced SHP2 phosphatase activity.
Implications:
- This discovery expands the spectrum of known PTPN11 mutations associated with LEOPARD syndrome beyond the two recurrent variants.
- It underscores the importance of screening the entire PTPN11 gene in LS patients who test negative for the common mutations.
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