Sorted By Test Name - Mayo Medical Laboratories

PTP22
89315
PTPN11 are missense mutations, although small deletions as well as whole gene duplications have been
reported to cause NS. Most mutations associated with NS destabilize the catalytically inactive
conformation of the protein, causing a gain of function of SHP-2. Some studies have shown that there is a
genotype-phenotype correlation associated with NS. An analysis of a large cohort of individuals with NS
has suggested that PTPN11 mutations are more likely to be found when pulmonary stenosis is present,
while hypertrophic cardiomyopathy (HCM) is commonly associated with RAF1 mutations but rarely
associated with PTPN11. Mutations in PTPN11 have also been identified in individuals with a variety of
other disorders that overlap phenotypically with NS. PTPN11 has been associated with LEOPARD
syndrome, an autosomal dominant disorder sharing several clinical features with NS and characterized by
multiple lentigines and cafe-au-lait spots, facial anomalies, and cardiac defects. Two mutations,
p.Tyr279Cys and p.Thr468Met, represent the most common PTPN11 mutations found in LEOPARD
syndrome, although other mutations have been described. Mutations in PTPN11 have also been identified
in patients who have clinical features of NS along with features of CFC syndrome, a condition involving
congenital heart defects, cutaneous abnormalities, Noonan-like facial features, and severe psychomotor
developmental delay. Genetic testing for PTPN11 mutations can allow for the confirmation of a suspected
genetic disease. Confirmation of NS or other associated phenotypes allows for proper treatment and
management of the disease and preconception, prenatal, and family counseling.
Useful For: Aiding in the diagnosis of PTPN11-associated Noonan syndrome and LEOPARD
syndrome
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Tartaglia M, Mehler E, Goldberg R, et al: Mutations in PTPN11, encoding
the protein tyrosine phophatase SHP-2, cause Noonan syndrome. Nat Genet 2001;29:465-468 2. Tartaglia
M, Kalidas K, Shaw A, et al: PTPN11 mutations in Noonan syndrome: molecular spectrum,
genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet 2002;70:1555-1563 3.
Musante L, Kehl H, Majewski F, et al: Spectrum of mutations in PTPN11 and genotype-phenotype
correlation in 96 patients with Noonan syndrome and 5 patients with cardio-facio-cutaneous syndrome.
Eur J Hum Genet 2002;11:201-206 4. Kontaridis M, Swanson K, David F, et al: PTPN11 (Shp2)
mutations in LEOPARD syndrome have dominant negative, not activating, effects. J Biol Chem
2006;281(10):6785-6792 5. Cohen MM, Gorlin RJ: Noonan-like/multiple giant cell lesion syndrome. Am
J Med Genet 1991;40:159 6. Lee JS, Tartaglia M, Gelb BD, et al: Phenotypic and genotypic
characterization of Noonan-like/multiple giant cell lesion syndrome. J Med Genet 2005;42(2):e11 7.
Tartaglia M, Gelb B, Zenker M: Noonan syndrome and clinically related disorders. Best Pract Res Clin
Endocrinol Metab 2011 Feb;25(1):161-179
PTPN22 Genotype, 1858C->T
Clinical Information: Rheumatoid arthritis (RA) is a systemic autoimmune disease that is
characterized by joint inflammation and destruction. It is heterogeneous, with genetic and environmental
factors contributing to its development.(1) There is a well-established link between an increased risk of
developing RA and specific alleles of the human leukocyte antigen (HLA) complex including
HLA-DRB1*0404, HLA-DRB1*0405, and HLA-DRB1*0101. It has been estimated that those HLA
alleles are responsible for approximately 50% of the genetic susceptibility to RA.(1) Recently, other genes
have been identified that also influence the susceptibility of an individual to developing RA. The gene
PTPN22 (protein tyrosine phosphatase, non-receptor type 22) encodes the protein Lyp, a phosphatase that
is responsible, in part, for regulating T-cell activation. A particular single nucleotide polymorphism (SNP)
in PTPN22, designated as 1858C->T, is found more frequently in individuals with autoimmune diseases,
including RA, than in healthy control cohorts.(2) It has been proposed that the 1858C->T SNP alters the
function of the Lyp, rendering the individual more susceptible to developing RA.(2) In addition, in
patients diagnosed with RA, the presence of the T allele has been linked to certain disease phenotypes,
including positivity for cyclic citrullinated peptide (CCP) antibodies (a marker for RA), earlier age at
diagnosis, and increased rate of joint erosion.(3)
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