Dermatology Hospital, Southern Medical University, Guangzhou, China.
Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Clin Exp Dermatol. 2019 Jun;44(4):e110-e117. doi: 10.1111/ced.13925. Epub 2019 Feb 7.
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.
To investigate the OSMR mutation spectrum in patients with sporadic (s)PLCA/fPLCA, lichen/macular PLCA in mainland China.
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.
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).
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.
原发性局限性皮肤淀粉样变（PLCA）是一种慢性瘙痒性皮肤病。家族性（f）PLCA 的遗传基础涉及抑瘤素 M 受体（OSMR）和白细胞介素-31 受体 A（IL31RA）基因的突变，但疾病的病理生理学尚未完全了解。
调查中国大陆散发性（s）PLCA/fPLCA、苔藓样/斑状 PLCA 患者中 OSMR 突变谱。
本研究纳入了 64 例 sPLCA 患者、36 例 fPLCA 患者和 10 名无血缘关系的个体，所有患者均来自 23 个无关的中国家庭。从外周血样本中提取基因组 DNA。通过 Sanger 测序对 17 个 OSMR 外显子进行突变筛查。
PLCA 病变通常局限于小腿、前臂和背部。OSMR 外显子序列分析显示，fPLCA 患者的 OSMR 错义突变率（63.89%）明显高于 sPLCA 患者（34.38%）。携带纯合 OSMR 突变的患者的男/女比例（0.29）明显低于携带杂合 OSMR 突变的患者（1.08；P<0.05）和携带野生型 OSMR 的患者（1.75；P<0.01）。携带 OSMR 纯合突变的 PLCA 患者的发病年龄（中位年龄 20 岁）早于携带 OSMR 杂合突变的 PLCA 患者（中位年龄 32 岁；P<0.01）和携带野生型基因型的 PLCA 患者（中位年龄 32 岁；P<0.01）。
本研究数据表明，OSMR 突变不仅是 fPLCA 的主要原因，也是 sPLCA 发病机制的潜在来源，尽管确切的分子机制尚不清楚。
