Clinical and genetic features of Chinese patients with lichen and macular primary localized cutaneous amyloidosis

Abstract

Summary Background Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic skin disorder. The genetic basis of familial (f)PLCA involves mutations in the oncostatin M receptor (OSMR) and interleukin‐31 receptor A (IL31RA) genes, but the disease pathophysiology is not fully understood. Aim To investigate the OSMR mutation spectrum in patients with sporadic (s)PLCA/fPLCA, lichen/macular PLCA in mainland China. Methods This study was carried out on 64 patients with sPLCA, along with 36 with fPLCA and 10 unaffected individuals collected from 23 unrelated Chinese families. Genomic DNA was extracted from peripheral blood samples. Mutation screening of 17 OSMR exons was performed by Sanger sequencing. Results PLCA lesions are typically localized to the shins, forearm and back. Sequence analysis of OSMR exons demonstrated that the OSMR missense mutation rate in patients with fPLCA (63.89%) was significantly higher than that in patients with sPLCA (34.38%). The male/female ratio of patients carrying a homozygous OSMR mutation (0.29) was significantly lower than that of patients carrying a heterozygous OSMR mutation (1.08; P < 0.05) and of patients with wildtype OSMR (1.75; P < 0.01). Age of onset of PLCA with OSMR homozygous mutation (median age 20 years) was earlier than that of PLCA with OSMR heterozygous mutation (median age 32 years; P < 0.01) or PLCA with wildtype genotype (median age 32 years; P < 0.01). Conclusion The present data indicate OSMR mutations as not only the main cause of fPLCA, but also the potential source of the pathogenesis of sPLCA, although the exact molecular mechanism remains unknown.

Primary Localized Cutaneous Amyloidosis of Keratinocyte Origin: An Update with Emphasis on Atypical Clinical Variants

“…This process can last from weeks to years, but once the first amyloid aggregation is formed, the development of the insoluble architecture soon follows [2]. With that said, the exact pathogenesis remains unclear, but it is considered to be multifactorial with both genetic and environmental risk factors associated with keratinocyte-derived amyloid formation [3].…”

“…Primary localized cutaneous amyloidosis appears to be mainly sporadic but in about 10% of patients, an autosomal dominant inheritance pattern with variable penetrance can be observed [4]. In addition, PLCA is common in southeast Asia, South America, and the middle eastern region [3]. The racial susceptibility and familial aggregation suggest that underlying genetic factors must play a role in the pathogenesis of PLCA.…”

OSMRβ mutants enhance basal keratinocyte differentiation via inactivation of the STAT5/KLF7 axis in PLCA patients

“…Recently, we demonstrated that the c.1538G>A (p.G513D) and c.2081C>T (p.P694L) mutations of OSMR were the most frequent mutations in a Chinese PLCA population (Lu et al, 2019 ). It has been reported that OSM maintains hair follicle stem cell and muscle stem cell quiescence by binding to heterodimeric receptors comprising gp130 and OSMRβ (Sampath et al, 2018 ; Wang et al, 2019 ).…”

A novel oncostatin M/interleukin‐31 receptor mutation in familial primary localized cutaneous amyloidosis

“…These are thought to arise from degenerate protein from basal keratinocytes, immunoglobulins and normal serum amyloid P component. Most cases are sporadic, with autosomal dominant inheritance responsible for about 10% of cases, and although common in South American and Asian populations, PLCA is rare in white populations.…”

“…Mutations in the genes for oncostatin M receptor ( OSMR ) and interleukin‐31 receptor A ( IL31RA ) have been previously reported in patients with PLCA . OSMR encodes for OSMR‐β, a member of the IL‐6 type cytokine receptor family, which binds IL‐31 and oncostatin M (OSM).…”