由SPINK5中的一个纯合子的移码突变产生的具有广泛脱屑及发育停滞的内瑟顿综合征  

Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK5

作　　者：Geyer A.S Ratajczak P Pol-Rodriguez M G. Richard 潘敏 

机构地区：[1]Thomas Jefferson University, Department of Dermatology and Cutaneous Biology,BLSB,233S.10th Street, Philadelphia,PA19107,United States.Dr

出　　处：《世界核心医学期刊文摘（皮肤病学分册）》2005年第10期55-55,共1页Digest of the World Core Medical JOurnals:Dermatology

摘　　要：Background:Netherton syndrome (NTS) is a rare autosomal recessive multisystem disorder characterized by congenital erythroderma and ichthyosis, hair shaft abnormalities and immune dysregulation. The disorder is caused by deleterious mutations in the SPINK5 gene, encoding the serine protease inhibitor LEKTI. Objective:Our objective was to investigate if the erythrodermic variant of peeling skin syndrome is also caused by SPINK5 mutations and to study the consequences of the disease on infantile brain development. Methods:In an infant with extensive erythroderma, peeling skin and failure to thrive, we analyzed the SPINK5 gene for pathogenic mutations by direct DNA sequencing and performed repeated brain MRI studies with diffusion-weighted imaging. Results:We identified a homozygous 4-base-pair insertion in exon 5 of SPINK5, which introduces a premature termination codon and appears to be a common mutation among West Indies islanders. MRI analyses revealed a persistent diffuse volume loss. Conclusion:Our results confirm that early truncation mutations of the coding sequence of SPINK5 produce a severe phenotype and that generalized peeling skin is one of the manifestations of NTS. We further demonstrate for the first time that NTS may be associated with MRI abnormalities indicative of a permanent tissue injury of the brain.Background:Netherton syndrome (NTS) is a rare autosomal recessive multisystem disorder characterized by congenital erythroderma and ichthyosis, hair shaft abnormalities and immune dysregulation. The disorder is caused by deleterious mutations in the SPINK5 gene, encoding the serine protease inhibitor LEKTI. Objective:Our objective was to investigate if the erythrodermic variant of peeling skin syndrome is also caused by SPINK5 mutations and to study the consequences of the disease on infantile brain development. Methods:In an infant with extensive erythroderma, peeling skin and failure to thrive, we analyzed the SPINK5 gene for pathogenic mutations by direct DNA sequencing and performed repeated brain MRI studies with diffusion-weighted imaging. Results:We identified a homozygous 4-base-pair insertion in exon 5 of SPINK5, which introduces a premature termination codon and appears to be a common mutation among West Indies islanders. MRI analyses revealed a persistent diffuse volume loss. Conclusion:Our results confirm that early truncation mutations of the coding sequence of SPINK5 produce a severe phenotype and that generalized peeling skin is one of the manifestations of NTS. We further demonstrate for the first time that NTS may be associated with MRI abnormalities indicative of a permanent tissue injury of the brain.

关 键 词：纯合子 SPINK5 移码突变 发育停滞 鱼鳞病样红皮病 红皮病型 弥散加权影像 基因突变 病由 常染色体隐性 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]