[PDF][PDF] PTPN11 mutations and genotype-phenotype correlations in Noonan and LEOPARD syndromes

T Ogata, R Yoshida - Pediatric Endocrinology Reviews, 2005 - academia.edu
T Ogata, R Yoshida
Pediatric Endocrinology Reviews, 2005academia.edu
TThis review summarizes PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11)
mutations and genotype-phenotype correlations in Noonan syndrome (NS) and LEOPARD
syndrome (LS). PTPN11 mutations have been identified in~ 40% of NS patients and in>
80% of LS patients. Since the vast majority of mutations reside in and around the broad
intramolecular interaction surface between the N-SH2 and PTP domains of the PTPN11
protein, they have been suggested to affect the intramolecular N-SH2/PTP binding in the …
Abstract
TThis review summarizes PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11) mutations and genotype-phenotype correlations in Noonan syndrome (NS) and LEOPARD syndrome (LS). PTPN11 mutations have been identified in~ 40% of NS patients and in> 80% of LS patients. Since the vast majority of mutations reside in and around the broad intramolecular interaction surface between the N-SH2 and PTP domains of the PTPN11 protein, they have been suggested to affect the intramolecular N-SH2/PTP binding in the absence of a phosphopeptide, leading to excessive phosphatase activities. The type of mutations is diverse in NS and limited in LS, and is almost mutually exclusive between NS and LS. Clinical assessment in NS patients implies that cardiovascular anomalies and hematologic abnormalities are predominant in mutation positive patients, hypertrophic cardiomyopathy is predominant in mutation negative patients, and growth deficiency, mental retardation, and minor somatic anomalies are similar between the two groups of patients. Phenotypic evaluation in LS patients suggests that a hypertrophic cardiomyopathy rather than an electrocardiographic conduction abnormality is characteristic of PTPN11 mutation positive patients.
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