A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome.
Noonan (NS) and multiple lentigines/LEOPARD syndromes (LS) have proved to be associated with distinct PTPN11 mutations. Noonan-like/multiple giant cell lesion syndrome (NLS) is a rare disease, characterised by short stature, facial dysmorphisms, congenital heart defect (CHD) and central giant cell lesions. PTPN11 gene mutations have been reported in a single NLS family and two sporadic patients. Here we report a patient with a complex phenotype progressing throughout the years from NS at birth towards LS and NLS. PTPN11 gene analysis disclosed a novel missense mutation (Ala461Thr) in exon 12, affecting the consensus sequence of the SHP2-active site. This observation joins together NS and LS to NLS into a unique genetic defect, broadening the clinical and molecular spectrum of PTPN11-related disorders.
CSS Hospital, IRCCS, San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy.
Anna
A
Sarkozy
Maria Gabriela
MG
Obregon
Emanuela
E
Conti
Giorgia
G
Esposito
Rita
R
Mingarelli
Antonio
A
Pizzuti
Bruno
B
Dallapiccola
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006225:Hand / Q000000981:diagnostic imaging; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D044542:LEOPARD Syndrome / Q000235:genetics*; D008334:Mandible / Q000002:abnormalities / Q000000981:diagnostic imaging; D009634:Noonan Syndrome / Q000235:genetics*; D017354:Point Mutation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011859:Radiography
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases