摘要目的:检测3个先天性鱼鳞病样红皮病家系基因突变情况。方法:对临床诊断为先天性鱼鳞病样红皮病的3例先证者外周血DNA进行遗传性皮肤病靶基因外显子测序明确突变位点，根据突变位点设计引物进行PCR扩增，Sanger测序验证先证者和家庭成员突变情况，明确致病原因。结果:先证者1和2表现为全身皮肤干燥，下肢伸侧多角形暗褐色鳞屑；先证者3主要表现为躯干、四肢境界清楚红斑、丘疹、鳞屑。均否认家族史。基因检测显示，先证者1存在PNPLA1基因c.100G>A（来自于母亲）和c.377G>A（来自于父亲）复合杂合突变；先证者2存在PNPLA1基因c.320T>A（来自于母亲）和c.434T>C（来自于父亲）复合杂合突变；先证者3存在PNPLA1基因上c.1300delG纯合突变。两个复合杂合突变家系表型和基因突变符合共分离原则。在检出的5个突变中，两个错义突变（c.377G>A和c.320T>A）为首次报道的突变。结论:PNPLA1基因的双等位基因突变是3个先证者的致病突变，新报道的突变丰富了该病基因突变谱。

abstractsObjective: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.