Ptpn11, which encodes tyrosine phosphatase SHP-2, is located on chromosome 12 (12q24.1) and expressed in most embryonic and adult tissues. It plays crucial roles in cell proliferation, differentiation, survival and cell death, participating in signaling events downstream of RAS-MAPK and JAK/STAT pathways [1].

Germline mutations in Ptpn11 cause Noonan syndrome (NS) and LEOPARD syndrome (LS), while somatic mutations contribute to leukemogenesis [3]. In NS-affected patients, Ptpn11 is one of the genes with a significant number of pathogenic variants. Clinical features in mutation-positive NS patients include congenital cardiac anomalies, short stature, pectus excavatum, and cryptorchidism in males [2]. A case of Noonan syndrome with protein-losing enteropathy was associated with a Ptpn11 mutation, though no clear genotype-phenotype correlation was found [4]. Ptpn11 mutations are also identified in a subset of human and canine disseminated histiocytic sarcoma, specifically the visceral disseminated form [5].

In conclusion, Ptpn11 is essential for multiple cellular processes through its involvement in key signaling pathways. Its mutations are strongly associated with NS, LS, and leukemogenesis, as well as some rare cancers like disseminated histiocytic sarcoma. Research on Ptpn11, especially through studying its mutations, provides insights into the mechanisms of these diseases, potentially guiding future diagnostic and therapeutic strategies.

References:

1. Xu, H Y, Yuan, Y Y, Dai, P. . [PTPN11 and the deafness]. In Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery, 33, 830-834. doi:10.13201/j.issn.1001-1781.2019.09.008. https://pubmed.ncbi.nlm.nih.gov/31446698/

2. Athota, Jeevana Praharsha, Bhat, Meenakshi, Nampoothiri, Sheela, Farooque, Mohammed Oomer, Shetty, Swathi. 2020. Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations. In BMC medical genetics, 21, 50. doi:10.1186/s12881-020-0986-5. https://pubmed.ncbi.nlm.nih.gov/32164556/

3. Tartaglia, Marco, Martinelli, Simone, Stella, Lorenzo, Emanuel, Peter D, Gelb, Bruce D. 2005. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. In American journal of human genetics, 78, 279-90. doi:. https://pubmed.ncbi.nlm.nih.gov/16358218/

4. Wang, Na, Shi, Wen, Jiao, Yang. 2020. A PTPN11 mutation in a woman with Noonan syndrome and protein-losing enteropathy. In BMC gastroenterology, 20, 34. doi:10.1186/s12876-020-01187-1. https://pubmed.ncbi.nlm.nih.gov/32054441/

5. Hédan, Benoit, Rault, Mélanie, Abadie, Jérôme, Donadieu, Jean, André, Catherine. 2020. PTPN11 mutations in canine and human disseminated histiocytic sarcoma. In International journal of cancer, 147, 1657-1665. doi:10.1002/ijc.32991. https://pubmed.ncbi.nlm.nih.gov/32212266/