| Background Porokeratosis is a group of disorders characterized by epidermal keratinization associated with a cornoid lamella, which is an autosomal dominant mode of inheritance. The typical lesions of porokeratosis were annular or like annular plaques with atrophic centers and peripheral keratotic ridge. Histopathologic examination showed unique characteristic of parakeratotic and hyperkeratotic cornoid lamella which points away from the center of the lesion. There were dyskeratotic cells and vacuolated keratinocytes below cornoid lamella. The granular layers beneath the column was usually absent or markedly reduced in thickness. Loose clusters of dyskeratotic cells or vacuolated keratinocytes may be seen in the spinous layer beneath cornoid lamella. A hundred years ago, Mibelli first found Mibelli porokeratosis (PM). In the same year, Respighi described a disseminated superficial porokeratosis (DSP). Subsequently, several other clinical variants of porokeratosis have been described: disseminated superficial actinic porokeratosis (DSAP), porokeratosis palmaris et plantaris disseminata (PPPD), linear porokeratosis and porokeratosis punctata palmaris et plantaris. Recently, porokeratosis were usuallyfound in transplantation, immunosuppressive therapy and HIV. Porokeratosis may be divided into three subtypes: a localized form, a disseminated form and immunosuppression induced porokeratosis.In six subtypes, it was rare that the coexistence of two variant porokeratosis in a patient or in a family. The age of onset was usually in the teens or first three decades of life in disseminated superficial porokeratosis. The arms, neck, trunk and face were commonly involved. The age of onset was before 20 years old in porokeratosis palmaris plantaris et dissminata. The lesions of PPPD were superficial papular lesions initially confined to the palms and soles with cornoid lamella. They are red to brown color and enlarge centrifugally over several months. The mature lesions are formed 4 to 5cm in diameter. The process is usually bilateral and symmetrical. After months or years, a secondary more generalized, eruption develops, particularly on the extremities and on the anterior and posterior trunk. The age of onset may be present at birth, childhood and early adulthood in linear porokeratosis. LP is characterized by the appearance of small, brown color and keratotic papules with atrophic centers and peripheral keratotic ridge. The lesions extend proximally and distantly to ultimately form a linear or zosteriform configuration. They are usually located over the limbs.Porokeratosis was an autosomal dominant mode of inheritance in DSP, DSAP, PM, PPPD and PPPP except LP. LP was coexistence with other variant porokeratosis. It shows that genetic factor was an important risk in porokeratosis. Such as transplantation, immunosuppressive therapy, sunlight exposure, trauma and infective agents, it can induce porokeratosis. In past, the progress of study the genes causedporokeratosis was slow. Recently, the gene scan was appeared and it was widely used, two loci for DSAP were mapping on 12q23.2-24.1 and 15q25.1-26.1 in two Chinese families by national laboratory of medical genetics of China. In contrast, so far there were no genes caused porokeratosis to be identified.Objectives To analyses the clinical and genetic features of DSP and PPPD and to identify the loci for DSP and PPPD. We will fine map loci in DSP and PPPD pedigrees, clone the disease gene of DSP and study its function.Methods Analysis the clinical and genetic features of DSP and PPPD through pedigrees with porokeratosis. Genotyping was performed in DSP and PPPD pedigrees using polymorphic microsatellite markers on loci of DSAP at 12q23.2-24.1 and 15q25.1-26.1. Followed by a genome-wide scan with 386 microsatellite markers from autosomes. Cloning disease gene of DSP using sequence. We will identify the size of DSP mRNA by RACE and study the expression of DSP through Northern.Results(1) In this study, there was coexistence of PPPD with DSP in PPPD pedigree and LP...
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