Familial primary localized cutaneous amyloidosis results from either dominant or recessive mutations in OSMR.

Abstract

© 2015 The Authors. doi: 10.2340/00015555-2104 Journal Compilation © 2015 Acta Dermato-Venereologica. ISSN 0001-5555 Primary localized cutaneous amyloidosis (PLCA; MIM 105250) is a chronic itchy skin disorder associated with amyloid deposits in the superficial dermis (1). Clinically, most skin lesions comprise small, flat-topped papules (lichen amyloidosis) or brown-grey macules (macular amyloidosis). Recently, proteins containing a considerable amount of β-sheet structures, such as galectin-7 and actin, have been reported as amyloidogenic in PLCA (2, 3). Most cases of PLCA are sporadic, but familial cases (FPLCA) with autosomal dominant inheritance also exist (4–6). Pathogenic mutations in OSMR and IL31RA have been reported as the major cause of FPLCA (5, 7); both of these genes belong to the family of interleukin (IL)6 family cytokine receptors. OSMR encodes oncostatin M receptor-beta (OSMRβ), a component of both the OSM type II receptor and the interleukin (IL)-31 receptor (8, 9), whereas IL31RA encodes the IL-31 receptor alpha, which combines with OSMRβ to form the IL-31 receptor (7). To date, 10 heterozygous missense mutations in OSMR and 1 heterozygous missense mutation in IL31RA have been reported in FPLCA, with all cases showing autosomal dominant inheritance (5–7, 10). In this study, we examined 2 large pedigrees with FPLCA originating from Pakistan (family A) and Malaysia (family B) (Fig. 1a, b). Unusually, however, the occurrence of FPLCA in both families is consistent with autosomal recessive, rather than dominant, inheritance.