Where are OSMR (Oncostatin M Receptor) mutations primarily found in primary localized cutaneous amyloidosis?

From the Research

OSMR mutations in primary localized cutaneous amyloidosis are primarily found in the extracellular fibronectin type III (FNIII) domains of the receptor, specifically affecting the regions critical for receptor dimerization and signaling function, as identified in studies such as 1 and 2. The mutations typically involve missense substitutions that alter the protein structure, affecting the ability of Oncostatin M to properly bind to its receptor and disrupting downstream signaling pathways. This disruption leads to abnormal keratinocyte differentiation and apoptosis, resulting in amyloid deposition in the papillary dermis. These genetic alterations have been identified predominantly in familial cases of primary localized cutaneous amyloidosis, particularly in families with macular and lichen amyloidosis, as noted in 1. The mutations appear to have an autosomal dominant inheritance pattern with variable penetrance, explaining why some family members with the mutation may show different clinical manifestations or severity of the disease. Some key points to consider include:

• The identification of OSMR mutations in primary localized cutaneous amyloidosis has provided new insights into the mechanisms of skin itching and amyloid deposition in the skin, as discussed in 2 and 1.
• The extracellular FNIII domains of the OSMR receptor are critical for receptor function and are the primary location of the mutations associated with primary localized cutaneous amyloidosis, as identified in 1.
• The treatment of primary localized cutaneous amyloidosis is not standardized, and various therapies have been reported to have varying degrees of efficacy, as noted in 3, 4, and 5. However, the most recent and highest quality study, 5, suggests that surgery is the most effective option for nodular amyloidosis and laser therapy is recommended for non-nodular patients. It's also worth noting that biologic agents and JAK inhibitors may be promising treatment options for lesions that do not respond to conventional therapies, as suggested in 5.