Germline variants in PTPN11 are the primary cause of Noonan syndrome with multiple lentigines (NSML) and Noonan syndrome (NS), which are both autosomal dominant congenital developmental disorders with high phenotypic variability that show substantial overlap in clinical features, such as facial dysmorphism, cardiovascular defects, hearing loss, and growth retardation. The NSML/NS phenotypes are extremely heterogeneous. Hearing loss is considered to be an infrequent feature in NSML/NS patients. However, in our cohort of 1,502 patients, we identified nine pathogenic variants of PTPN11 in 10 probands (0.67%, 10/1,502), in which congenital sensorineural hearing loss (SNHL) was the main manifestation. Therefore, screening for PTPN11 variants in patients with congenital SNHL is recommended, even if they do not present with the typical features of NSML or NS. This study further showed PTPN11’s ubiquitous expression pattern in mice inner ear, and the underlying mechanisms thereof, in the auditory system. We speculate that disturbance of the Wnt/β–catenin signaling pathway may play a role in the signaling mechanisms involved in NSML/NS–related hearing loss. (By Dr. Xue Gao, https://jmg.bmj.com/content/early/2020/07/31/jmedgenet-2020-106892 )
Congenital sensorineural hearing loss as the initial presentation of PTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: clinical features and underlying mechanisms
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