MST1R Mutation As a Genetic Cause of Lady Windermere Syndrome

The prevalence of pulmonary nontuberculous mycobacterial (pNTM) disease is increasing [1]. The most commonly isolated disease-causing NTMs belong to the Mycobacterium avium complex [1]. Susceptibility to and clinical manifestation of NTM disease are largely governed by the immune status of a person. Disseminated or extrapulmonary NTM infections are strongly associated with severe immunosuppression, such as those with frank defects in the interferon (IFN)-γ–interleukin (IL)-12 axis [2]. Isolated pNTM is strongly associated with certain underlying conditions, such as cystic fibrosis, chronic obstructive pulmonary disease and primary ciliary dyskinesia [3, 4]. However, substantial numbers of pNTM patients have no apparent risk factors, and a significant proportion of them exhibit a body morphotype characterised by lifelong slender body habitus, pectus excavatum, scoliosis and mitral valve prolapse [5, 6], also called the Lady Windermere syndrome. A modest reduction in IFN-γ production and an increase in transforming growth factor (TGF)-β levels have been described [7–10]. Fowler et al. [11] quantified ciliary beat frequency of 58 pNTM patients and 40 controls and found reduced ciliary beat frequency in the pNTM patients. Szymanski et al. [12] performed whole-exome sequencing on patients with pNTM, their unaffected family members and a control group and concluded that pNTM is a multigenic disease, encompassing potential defects in proteins encoded by cilia genes, the cystic fibrosis transmembrane conductance regulator gene, connective tissue genes and certain immune-related genes. Susceptibility to NTM infections in patients with Lady Windermere syndrome is associated with MST1R variants http://ow.ly/xKgX304uhse