关键词: 鳞癣样红皮病, 先天性, 先天性常染色体隐性遗传性鱼鳞病, PNPLA1基因, 复合杂合突变

Abstract: 【Abstract】 Objective To detect gene mutations in 3 Chinese families with congenital ichthyosiform erythroderma. Methods Exome sequencing of peripheral blood DNA was performed for 3 probands clinically diagnosed with congenital ichthyosiform erythroderma by using a gene panel targeting hereditary skin diseases to identify mutation sites. Primers were designed according to the mutation sites for PCR amplification, and Sanger sequencing was performed to verify the mutations in probands and other family members in order to identify the cause of the disease. Results The probands 1 and 2 presented with generalized skin dryness and scaling, and polygonal dark brown scales on the extensor aspect of the lower limbs; the proband 3 mainly presented with well-circumscribed erythema, papules and scales scattered on the trunk and extremities. All probands denied family history of similar diseases. Genetic testing showed that the proband 1 carried compound heterozygous mutations c.100G>A and c.377G>A in the PNPLA1 gene, which were inherited from her mother and father respectively; the proband 2 carried compound heterozygous mutations c.320T>A and c.434T>C in the PNPLA1 gene, which were inherited from her mother and father respectively; a homozygous mutation c.1300delG was identified in the PNPLA1 gene in the proband 3. The mutations co-segregated with the disease phenotypes in the two families with compound heterozygous mutations. Among the 5 identified mutations, the two missense mutations （c.377G>A and c.320T>A） were firstly reported. Conclusion Biallelic mutations in the PNPLA1 gene are the causative mutations responsible for autosomal recessive congenital ichthyosis in the three probands, and the newly reported mutations expand the mutation spectrum in the disease.

Key words: Ichthyosiform erythroderma, congenital, Autosomal recessive congenital ichthyosis, PNPLA1 gene, Compound heterozygous mutation