Neutral lipid storage disease with ichthyosis (NLSDI; Chanarin-Dorfman syndrome) is an ichthyosiform syndrome, often associated with mutations in a lipid hydrolase, CGI-58. The presence of oil red O-positive, neutral ...Neutral lipid storage disease with ichthyosis (NLSDI; Chanarin-Dorfman syndrome) is an ichthyosiform syndrome, often associated with mutations in a lipid hydrolase, CGI-58. The presence of oil red O-positive, neutral lipid droplets in tissue biopsies, and/or in leukocytes on blood smears, coupled with a constellation of multisystem abnormalities and a pruritic ichthyosiform erythroderma, are together diagnostic of NLSDI. We investigated the pathogenesis of the ichthyosiform erythroderma in patients from three unrelated kindreds with a clinical diagnosis of NLSDI. Basal permeability barrier function and stratum corneum (SC) integrity were abnormal, but barrier recovery rates were faster than normal, as in atopic dermatitis. The basal barrier abnormality was linked to the secretion of lipid micro-inclusions, first segregated within lamellar bodies (LB), which then form a non-lamellar phase within the SC interstices, shown by combined ruthenium tetroxide post-fixation and lipid-retaining resin-white embedding. With colloidal lanthanum nitrate perfusion, excess water/solute movement was restricted to the SC interstices, and further localized to non-lamellar domains. Phase separation of excess stored lipid provides a unifying pathogenic mechanism not only for NLSDI, but also in several other inherited ichthyosiform disorders of lipid metabolism, such as recessive X-linked ichthyosis and type 2 Gaucher’s disease.展开更多
10号染色体上磷酸酶和张力蛋白同源物(phosphatase and tensin-homolog deleted on chromosome 10,PTEN)是重要的抑癌基因,其突变可引发PTEN错构瘤肿瘤综合征(PTEN hamartoma tumor syndrome,PHTS),常被称为Cowden综合征,是较为罕见的...10号染色体上磷酸酶和张力蛋白同源物(phosphatase and tensin-homolog deleted on chromosome 10,PTEN)是重要的抑癌基因,其突变可引发PTEN错构瘤肿瘤综合征(PTEN hamartoma tumor syndrome,PHTS),常被称为Cowden综合征,是较为罕见的遗传性肿瘤综合征,其与早发性、多发性乳腺癌高度相关。本文报道3例PTEN基因突变相关单侧多中心乳腺癌及同时性、异时性双侧乳腺癌患者,并总结其临床表现、病理特征、诊治经验及随访情况,旨在为临床医生更好地诊治PTEN基因突变相关乳腺癌及Cowden综合征人群提供借鉴。展开更多
文摘Neutral lipid storage disease with ichthyosis (NLSDI; Chanarin-Dorfman syndrome) is an ichthyosiform syndrome, often associated with mutations in a lipid hydrolase, CGI-58. The presence of oil red O-positive, neutral lipid droplets in tissue biopsies, and/or in leukocytes on blood smears, coupled with a constellation of multisystem abnormalities and a pruritic ichthyosiform erythroderma, are together diagnostic of NLSDI. We investigated the pathogenesis of the ichthyosiform erythroderma in patients from three unrelated kindreds with a clinical diagnosis of NLSDI. Basal permeability barrier function and stratum corneum (SC) integrity were abnormal, but barrier recovery rates were faster than normal, as in atopic dermatitis. The basal barrier abnormality was linked to the secretion of lipid micro-inclusions, first segregated within lamellar bodies (LB), which then form a non-lamellar phase within the SC interstices, shown by combined ruthenium tetroxide post-fixation and lipid-retaining resin-white embedding. With colloidal lanthanum nitrate perfusion, excess water/solute movement was restricted to the SC interstices, and further localized to non-lamellar domains. Phase separation of excess stored lipid provides a unifying pathogenic mechanism not only for NLSDI, but also in several other inherited ichthyosiform disorders of lipid metabolism, such as recessive X-linked ichthyosis and type 2 Gaucher’s disease.
文摘10号染色体上磷酸酶和张力蛋白同源物(phosphatase and tensin-homolog deleted on chromosome 10,PTEN)是重要的抑癌基因,其突变可引发PTEN错构瘤肿瘤综合征(PTEN hamartoma tumor syndrome,PHTS),常被称为Cowden综合征,是较为罕见的遗传性肿瘤综合征,其与早发性、多发性乳腺癌高度相关。本文报道3例PTEN基因突变相关单侧多中心乳腺癌及同时性、异时性双侧乳腺癌患者,并总结其临床表现、病理特征、诊治经验及随访情况,旨在为临床医生更好地诊治PTEN基因突变相关乳腺癌及Cowden综合征人群提供借鉴。