A 4-year-old boy presents with short stature (height <3rd percentile), characteristic facial features including hypertelorism and downslanting palpebral fissures, webbed neck, and a systolic ejection murmur. Echocardiography reveals dysplastic pulmonary valve stenosis. Genetic testing identifies a gain-of-function mutation at the locus marked **A** (12q24.13). Which of the following best describes the molecular consequence of this mutation in Noonan syndrome?

The locus marked A at 12q24.13 corresponds to PTPN11, which encodes the SHP-2 tyrosine phosphatase. Gain-of-function mutations in PTPN11 account for approximately 50% of Noonan syndrome cases and represent the most common genetic cause. The pathophysiology involves enhanced RAS-MAPK pathway signaling, not loss of function. In Noonan syndrome, the mutant SHP-2 protein acquires increased catalytic activity or altered substrate specificity, leading to dysregulated activation of downstream RAS-MAPK signaling. This enhanced signaling causes the characteristic features seen in this patient: short stature, distinctive facies, cardiac anomalies (particularly dysplastic pulmonary stenosis in 50-60% of cases), and lymphatic dysplasia. The clinical presentation—short stature, hypertelorism, downslanting palpebral fissures, webbed neck, and dysplastic pulmonary valve stenosis—is pathognomonic for Noonan syndrome and directly reflects the consequences of RAS-MAPK pathway hyperactivation. Molecular testing confirming a PTPN11 mutation at 12q24.13 establishes the diagnosis and explains the gain-of-function mechanism underlying this RASopathy.