PDF(Pubmed)
Abstract：
BACKGROUND: Mutations in the KRT1 gene encoding keratin 1 cause epidermolytic hyperkeratosis characterized by blistering in the neonatal period followed by ichthyotic hyperkeratosis in childhood and adolescent life. We observed a spectrum of clinical manifestations of blistering disorders caused by different mutations in the same KRT1 gene.
OBJECTIVE: To analyse the phenotypic spectrum of blistering disorders caused by the KRT1 mutations.
METHODS: Four patients with an epidermal barrier defect manifesting as blistering with the KRT1 mutations were included to the study. The clinical course of the disease was analysed, histology, immunofluorescence and electron microscopic examinations were performed.
RESULTS: An adult patient with severe ichthyosis with p.Asn188Lys mutation in exon 1 of KRT1 who occasionally develops blisters in adolescence represents epidermolytic hyperkeratosis, a newborn child who died 4 days after birth due to disruption of the epidermal barrier (extensive blister and erosions) with mutation p.Ser193Pro in the KTR1 gene and two adult sisters harbouring heterozygous mutation c.591+1A>G in the KRT1 gene who present superficial blisters induced by mild trauma from the birth up to adolescent life without ichthyosis suggesting the diagnosis of epidermolysis bullosa simplex. Histopathology in all adult patients showed cytoplasm disruption in keratinocytes of the stratum spinosum with keratohyalin granule-like structures and, on the ultrastructural level, the presence of keratin clumping confirming the pathology of keratin intermediate filaments.
CONCLUSIONS: This study extends the knowledge of the clinical spectrum for the KRT1 gene mutations. This is the first description of familial dominant epidermolysis bullosa simplex linked to the KRT1 mutation.
OBJECTIVE: To analyse the phenotypic spectrum of blistering disorders caused by the KRT1 mutations.
METHODS: Four patients with an epidermal barrier defect manifesting as blistering with the KRT1 mutations were included to the study. The clinical course of the disease was analysed, histology, immunofluorescence and electron microscopic examinations were performed.
RESULTS: An adult patient with severe ichthyosis with p.Asn188Lys mutation in exon 1 of KRT1 who occasionally develops blisters in adolescence represents epidermolytic hyperkeratosis, a newborn child who died 4 days after birth due to disruption of the epidermal barrier (extensive blister and erosions) with mutation p.Ser193Pro in the KTR1 gene and two adult sisters harbouring heterozygous mutation c.591+1A>G in the KRT1 gene who present superficial blisters induced by mild trauma from the birth up to adolescent life without ichthyosis suggesting the diagnosis of epidermolysis bullosa simplex. Histopathology in all adult patients showed cytoplasm disruption in keratinocytes of the stratum spinosum with keratohyalin granule-like structures and, on the ultrastructural level, the presence of keratin clumping confirming the pathology of keratin intermediate filaments.
CONCLUSIONS: This study extends the knowledge of the clinical spectrum for the KRT1 gene mutations. This is the first description of familial dominant epidermolysis bullosa simplex linked to the KRT1 mutation.
摘要：
背景：编码角蛋白1的KRT1基因中的突变导致表皮性角化过度，其特征是在新生儿期出现水疱，然后在儿童和青少年时期出现鱼鳞病性角化过度。我们观察到由同一KRT1基因中的不同突变引起的起泡性疾病的临床表现谱。
目的：分析KRT1突变引起的水疱性疾病的表型谱。
方法：本研究纳入了4例表皮屏障缺损患者，表现为KRT1突变的起泡。分析了该疾病的临床病程，组织学,进行免疫荧光和电子显微镜检查。
结果：患有严重鱼鳞病的成人患者，在KRT1的外显子1中出现p.Asn188Lys突变，在青春期偶尔会出现水疱，代表表皮角化过度，1名新生儿在出生后4天因表皮屏障破坏（广泛的水疱和糜烂）而死亡，KTR1基因中的p.Ser193Pro突变和KRT1基因中的两个成年姐妹具有杂合突变c.5911A>G，从出生到青春期的轻度创伤引起浅表水疱，没有鱼鳞病，提示诊断为单纯大疱性表皮松解症。所有成年患者的组织病理学均显示，棘层角质形成细胞的细胞质破裂，并伴有角质透明蛋白颗粒样结构，在超微结构层面上，角蛋白凝块的存在证实了角蛋白中间丝的病理学。
结论：本研究扩展了KRT1基因突变的临床范围。这是与KRT1突变相关的家族性显性大疱性表皮松解症的首次描述。
目的：分析KRT1突变引起的水疱性疾病的表型谱。
方法：本研究纳入了4例表皮屏障缺损患者，表现为KRT1突变的起泡。分析了该疾病的临床病程，组织学,进行免疫荧光和电子显微镜检查。
结果：患有严重鱼鳞病的成人患者，在KRT1的外显子1中出现p.Asn188Lys突变，在青春期偶尔会出现水疱，代表表皮角化过度，1名新生儿在出生后4天因表皮屏障破坏（广泛的水疱和糜烂）而死亡，KTR1基因中的p.Ser193Pro突变和KRT1基因中的两个成年姐妹具有杂合突变c.5911A>G，从出生到青春期的轻度创伤引起浅表水疱，没有鱼鳞病，提示诊断为单纯大疱性表皮松解症。所有成年患者的组织病理学均显示，棘层角质形成细胞的细胞质破裂，并伴有角质透明蛋白颗粒样结构，在超微结构层面上，角蛋白凝块的存在证实了角蛋白中间丝的病理学。
结论：本研究扩展了KRT1基因突变的临床范围。这是与KRT1突变相关的家族性显性大疱性表皮松解症的首次描述。
