Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome.

Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome.
J Pediatr Hematol Oncol. 2008 Aug
Laux D, Kratz C, Sauerbrey A.
Pediatric Hematology and Oncology Unit, Department of Pediatrics, HELIOS Klinikum Erfurt, Erfurt, Germany. danilaux@yahoo.de

Germline mutations in PTPN11 gene cause Noonan syndrome and the clinically similar LEOPARD syndrome (LS). LS is a rare congenital developmental disorder characterized by multiple lentigines, cardiac abnormalities, facial dysmorphism, retardation of growth, and deafness. Mutations in exons 7 and 12 of the PTPN11 gene can be identified in nearly 90% of patients with LS. PTPN11 gene encodes for an ubiquitously expressed protein tyrosine phosphatase SHP-2 involved in a variety of intracellular signaling processes in development and hematopoiesis. Somatic PTPN11 mutations contribute to leukemogenesis in children with hematologic malignancies including juvenile myelomonocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and myelodysplasia. Two cases of leukemia (acute myeloid leukemia) have been reported in children with LS. The authors describe for the first time a girl with genetically confirmed LEOPARD syndrome presenting with common acute lymphoblastic leukemia.

PMID: 18799937 [PubMed - indexed for MEDLINE]

Mutational Analysis of PTPN11 Gene in Taiwanese Children with Noonan Syndrome

Mutational Analysis of PTPN11 Gene in Taiwanese Children with Noonan Syndrome

Key Words: mutation analysis, Noonan syndrome, PTPN11, SHP-2

Noonan syndrome (NS) is an autosomal dominant disorder presenting with characteristic facies, short stature, skeletal anomalies, and congenital heart defects. Mutations in protein-tyrosine phosphatase, nonreceptor-type 11 (PTPN11), encoding SHP-2, account for 33–50% of NS. This study screened for mutations in the PTPN11 gene in 34 Taiwanese patients with NS. Mutation analysis of the 15 coding exons and exon/intron boundaries was performed by polymerase chain reaction and direct sequencing of the PTPN11 gene.

We identified 10 different missense mutations in 13 (38%) patients, including a novel missense mutation (855T>G, F285L). These mutations were clustered in exon 3 (n = 6) encoding the N-SH2 domain, exon 4 (n = 2) encoding the C-SH2 domain, and in exons 8 (n = 2) and 13 (n = 3) encoding the PTP domain. In conclusion, this study provides further support that PTPN11 mutations are responsible for Noonan syndrome in Taiwanese patients.

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