Abstract: Gao Dong, Lian Peiwen, Chen Jian, Ma Xianying, Zhou Surong. Yantai Yuhuangding Hospital, Yantai 264000, Shandong, China Corresponding author: Chen Jian, Email: jianchen2005@gmail.com 【Abstract】 Objective To report a family with lipoid proteinosis （LP） from Shandong province and to analyze mutations in the extracellular matrix protein 1 （ECM1） gene in this family. Methods Eight members in a three-generation family with LP were clinically investigated, and two patients were identified to suffer from LP, including the proband （Ⅲ1） and her mother （Ⅱ2）. Both of the patients presented with papules on the palpebral margin, short and thick lingual frenum, and hoarseness. Indirect laryngoscopy showed infiltrating and thickening of the vocal cord. Pathological examination of lesions on the palpebral margin and laryngeal mucosa revealed deposits of hyaline-like material in the dermis, which was strongly positive for periodic acid-Schiff （PAS） staining and resistant to diastase digestion. The pathological diagnosis was LP. Blood samples were collected from all the family members and 100 ethnically matched, unrelated and unaffected Chinese human controls followed by DNA extraction. PCR and sequencing were performed to detect the ECM1 gene, and nested PCR followed by agarose gel electrophoresis to analyze mutations in the coding region of the ECM1 gene. Results Both of the two patients were compound heterozygotes. Three missense mutations, incluing p.P169T, p.A44T and p.R392W, were found in the ECM1 gene of the affected mother, with p.P169T in one allele and p.A44T as well as p.R392W in the other. The girl patient inheried the missence mutation p.P169T from her mother and a synonymous mutation c.879G > A from her father （Ⅱ1）. Nested PCR showed that the c.978G > A mutation generated a splice-acceptor site "AG", which leaded to a splicing defect. Conclusion A novel synonymous splice-acceptor site mutation c.879G > A in the ECM1 gene is identified in the family with LP.

Key words: Lipoid proteinosis of Urbach and Wiethe, Extracellular matrix proteins, Mutation