| Porokeratosis is a group of inheritable skin diseaseand and its pathogenesis remains elusive. Porokeratosis contains clinically at least five different variants, that is, disseminated superficial actinic porokeratosis (DSAP, MIM 175900), classic porokeratosis of Mibelli (PM, MIM 175800), porokeratosis plantaris, palmaris, et disseminata( PPPD, MIM 175850), porokeratosis punctata palmaris et plantaris (PPPP, MIM 175860) and linear porokeratosis (LA); however, there are no clear-cut clinical or histological criteria to differentiate one variant from another, and thus all these presentations could merely be recognized as the identical disease before the underlying-gene mapping and cloning of porokeratosis is completed. The goals of this paper were to study on the uniformity and heterogeneity of th clinic and genetics of porokeratosis using pedigree analysis and two-point linkage analysis.At first, we paid much attention to the proband with porokeratosis in his presentations and histopathology. After having taken skin specimen from the probands of the five pedigrees to diagnose clinically as porokeratosis, respectively, medical examination were done for every living family members of the five pedigrees, and the data of clinic and genetics were collected for research into the characteristics of porokeratosis. Secondly, the Peripheral bJood samples were taken from available PPPD family members aged above 10 y, and genomic DNA was extracted from peripheral leukocytes using a Qiagen Kit (QIAGEN Company) according to the manufacturer's protocol. Twelve polymorphic microsatellite markers were selected from the long arm of chromosome spanning through the region of 12q23-24 where DSAP was mapped. The intervals of these markers averages from 5cM to 12cM. Programs MLINK and ILINK from the LINKAGE package were used in linkageanalysis to calculate two-point LOD scores (z) for a recombination distance ( 9 ).By analysis of the clinic and genetics data, some findings were that: l)the five pedigrees belonged to three variants of porokeratosis, consisting of three DSAP pedigrees (totally 266 family members including 100 patients), and one PPPD pedigree (containing 90 family members including 26 patients), and one PM pedigree (composing of 34 members including 17 patients). 2)The five pedigrees held some common feature that: all inherited in an autosomal dominant pattern, and all had clinical lesions with a distinct annular or gyrate plaques with an atrophic center and a prominent peripheral ridge, and had histologically a cornoid lamella of porokeratosis, a parakeratotic column, located above a dell in the surface of the epidermis. 3)on the hand, the heterogeneity of poroketatosis showed that the five pedigrees belonged to three variants, namely disseminated superficial actinic porokeratosis (DSAP), Porokeratosis plantaris et disseminata (PPPD), Porokeratosis of Mibelli (PM). Furthermore, every variants had itself features that (1)the DSAP variant consisting of three pedigrees was the common subtype, the onset of age (generally 9 y~15y) was earlier than the two other variant, and the onset lesion was only on the sun-exposed face; (2)As to the rare PPPD variant, the. onset of age varied from 14 y to 20 y, and the lesion appeared to first involve in the palms and soles, (3)finally, the onset of age for the PM variants was most latest (from 20 y to 30 y) than the two former, and the onset lesion was not a fixed part on the body, such as upper arm, lower extremities, the back of hand, the forehead, the front-area of ear and so on. (4)To our most interested, in the PPPD pedigree, Among the 20 affected individuals examined by experienced dermatologist, only 5 patients tended to first occur on the palms and soles, and subsequently spread the distal parts of the limbs, the face, and the lower extremities and finally over the body. But for the others the onset lesion appeared on the face or the upper limbs, but not on the palms or soles. As to the PM pedigree, among the 17 patients examined, only the proband (aged 14 y) presented with...
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