Gene: [17q2/PSORS2] psoriasis susceptibility locus 2 (psoriasin?); [PSOR ]
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COM |
[1] The chromosome location of PSORS2 was suggested on the basis of data
obtained by an indirect method evaluating genetic linkage between the
disease phenotype and polymorphic microsatellite markers. Since the data
related to regional locations of the latter are approximate (see the
option 'Chromosome_location' in the given entry), direct methods should
be applied to define finally the exact location of PSORS2.
[2] Another gene (psoriasis susceptibility locus 1) was also deduced by an indirect method evaluating associations between the phenotype and particular HLA antigenes (GEM:06p213/PSORS1). [3] About psoriasin 1 (S100 calcium-binding protein A7) see GEM:01q21/S100A7." |
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LOC |
[1] As a result of a large-scale gene linkage search for psoriasis in
eight multiplex families, the Anne Bowcock's group from University of
Texas Southwestern Medical Center has revealed highly significant
linkage of the disease phenotype with several micrositellite markers
previously mapped to Chr 17q, particularly in the segment q23-25.
According to the published data (Tomfohrde-1994), a genetic distance
map of the segment involved can be presented as follows:
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-> 0.11 <-
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[2] In addition, the authors tested for linkage of psoriasis with HLA antigenes. They found that only two families (among those in which the disease was unlinked to Chr 17q) provided some data supporting that another psoriasis susceptibility locus possibly exists and may be associated with HLA-Cw6 (also see GEM:06p213/PSORS1)." |
|
PHE |
[1] The classic clinical description of psoriasis has been given by
R. Willian, in 1801; but, as a particular pathological entity
distinguished from leprotic and similar skin lesions, the condition has
been defined first by the Viennese physician von Hebra in 1841.
[2] Currently, psoriasis is being defined as a chronic, noncontagious disease characterized by multiple skin lesions such as erythematous papules (maculopapules) and plaques often covered with some kind of scale-like hyperkeratotic thickenings. The lesions, often symmetrical, occur on various parts of the body and extremities (including nails) as well as scalp, ears, neck, and not rare mucous membranes of lips, the mouth, the tongue, and the glance penis. The lesions are sharply demarcated with clear-cut borders. Under the scale-like thickenings, the skin exhibits the Auspitz sign when the scales are removed by scratching - within a few seconds, small blood droplets appear on the glossy, homogeneously erythematous surface. The other important sign is the Koebner reaction that means a manifestation of typical psoriatic lesions at sites of accidental skin injuries - scratches, eruptions, and burns. Internal organs never were shown to be affected in psoriasis; and psoriatic arthropathies are the only concomitant conditions. [3] A number of particular clinical and histopathological patterns of psoriatic manifestations have been described. All of them can be considered as varieties of two main histopathological types - chronic plaque and eruptive (pustular, guttate) psoriasis. Based on joint clinical and morphological criteria, the following commonly occurring forms of psoriasis were described: Chronic stationary psoriasis vulgaris; Psoriatic erythroderma; Generalized (acute) pustular and Localized pustular forms. The latter occurs as two distinct varieties - palmoplantar variant of Barber, and acrodermatitis continua of Hallopeau. Among the other forms, occurring infrequently, Annular pustular psoriasis and those occurring before puberty should be mentioned. The latter occurs as three distinct varieties - Follicular, Acute guttate, and Localized scalp psoriasis. [4] Causes and pathogenic mechanisms of the multiformity of psoriatic lesions are yet unclear. Based on clinical and histopathological criteria, some authors (see the reference (3) in [5]) considered all of the mentined forms of psoriasis in frames of a nosological entity. At the same time, results obtained by the HLA antigenes-psoriasis association studies showed that genetic heterogeneity of the disease is a probable phenomenon. For example, any individual having the HLA antigenes B13 or B17 has a fivefold risk of developing psoriasis, particularly guttate and erythrodermic forms of the disease; whereas HLA B8, Bw35, Cw7, and possibly DR3 were increased in palmaplantar pustular psoriasis. An essential role of hereditary predispositon to the condition was demonstrated by a number of studies (see the option 'formal_genetics'). So far, however, power methods of the genetic correlational analysis were yet not applied to test whether suggestions on genetic heterogeneity or, contrary, homogeneity of psoriasis are true. [5] For detailed information on the clinical subject matters, see the following textbooks: (1) Clinical Dermatology. 21st revision, 1994. Eds: D.J.Demis et al., J.B.Lippincott C., Philadelphia, Vol.1, Section 1 (1-4). (2) Andrews' Diseases of the skin. 8th ed, 1990. Eds: H.L.Arnold et al., W.B.Saunders C., Philadelphia, Chapt.10 (pp.198-226). (3) Dermatology in General Medicine. 3rd ed, 1987. Eds: T.B.Fitzpatrick et al., McGraw-Hill C., NY, Vol.1, Chapters 42-43 (pp. 461-501)." |
|
FOG |
[1] Prevalence rates of psoriasis widely vary in different ethnic
groups and is reported to range from 0.1% to 3%. For example, in
the USA the rates vary from single cases (possibly questionable)
in American Indians and 0.1% in Afro-Americans (most of whom are
descended from West African natives) to 1.5% in American whites.
Psoriasis is a condition as common among East African natives as
in North European natives, among which the prevlence ranges from
1.3% in Germany, 1.6% in Great Britain, 1.7% in Denmark, to 2.3%
in Sweden. On the other hand, the rates are definitely low in Eskimos
and Japanese.
Psoriasis occurs with similar frequency in both sexes. However, the data
deals with the total prevalence rates, and not differential rates in
various forms of the disease. It could be important to test a hypothesis
that the gender is not one of essential factors involved in the
pathogenesis
of psoriasis by comparing male/female rates in different clinical forms of
the disease.
Although psoriatic lesions may develop first both just at birth and even
at age after 100, the majority of patients develop the initial symptoms
in the second to fourth decades of life, with the mean age of onset being
around 25-28 in general populations.
[2] According to the majority of authors, hereditary factors are essentially involved in the pathogenesis of psoriasis. The following facts support such a conclusion: 1) a higher rate of concordance for the disease among monozygotic twins (65%) than in dizygotic twin pairs (30%); 2) an increased prevalence of psoriasis among relatives of affected probands (6.4%) in comparing with that (1.5%) in the general population; 3) a proportional increase of the prevalence (7.5%, 15%, and 50%) in offspring of matings where neither parent, only one, or both parents are affected, correspondingly. On the other hand, the specific mode of family transmission has not been established for the disease although some of the Mendelian models (simple autosomal dominance with incomplete penetrance and double autosomal recessive) were tested. This fact is a general feature of many multifactorial diseases; and probably means that a kind of genetic heterogeneity, or some uncommon genetic mechanisms are involved in etiology and pathogenesis of psoriasis. As noted in [4] (see the option 'Phenotype'), some of the reported, especially strong associations of HLA antigenes with psoriasis can be considered as a support of the heterogeneity hypothesis. Such associations possibly mean that another psoriasis susceptibility locus may reside on the the same chromosome segment 6p21.3 where the HLA complex genes reside (see GEM:06p213/PSORS1). [3] Based on the fact that psoriasis is probably a T cell-mediated, autoimmune disorder, Tomfohrde-1994 suggested that at least one factor mapped on the same 17q distal region might be considered as a highly probable candidate gene - interleukin enhancer binding factor (GEM:17q25/ILF1). This factor binds to purine-rich regions of the interleukin-2 and human immunodeficiency virus promoters; and hence, if a mutation in ILF may alter its regulation of IL-2 transcription, then inappropriate expression of the latter 'could result in the inflammatory cascade and hyperproliferation characteristic of lesional skin'. [4] In addition to the Main reference list in this entry, also see the following publications: (1) Lomholt G. Psoriasis: Prevalence, Course and Genetics. In: A Census Study on the Prevalence of Skin Disease on the Faroe Islands. Copenhagen, GEC Gad, 1963, pp. 163. (2) Farber E.M., Nall M.L. Genetics of psoriasis (twin study). In E.M.Farber, A.J.Cox (eds), Psoriasis (International Symposium), Stanford Univ Press, 1971, pp. 7-13." |
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REF |
FOG "Abele &: Arch Derm, 88, 38-47, 1963 ASS,LIN "Beckman &: Hum Hered, 24, 496-506, 1974 FOG "Burch, Rowell: Arch Derm, 117, 251-252, 1981 FOG "Farber &: Arch Derm, 109, 207-211, 1974 FOG "Happle R: J Med Genet, 28, 337, 1991 FOG "Kimberling, Dobson: J Invest Derm, 60, 538-540, 1973 FOG "Moll, Wright: Ann Rheum Dis, 32, 181-201, 1973 ASS,LIN "Pietrzyk &: Arch Derm Res, 273, 287-294, 1982 ASS,LIN "Russell &: New Engl J Med, 287, 738-740, 1972 MEB,PAT "Saiag &: Science, 230, 669-672, 1985 FOG "Steinberg &: AJHG, 4, 373-375, 1952 FOG "Steinberg &: AJHG, 3, 267-281, 1951 ASS,LIN "Suarez-Almazor, Russell: Arch Derm, 126, 1040-1042, 1990 LOC,LIN,MOL,MAG "Tomfohrde J &: Science, 264, (May 20), 1141-1145, 1994 FOG "Ward, Stephens: Arch Derm, 84, 589-592, 1961 FOG "Watson &: Arch Derm, 105, 197-207, 1972 ASS,LIN "White &: New Engl J Med, 287, 740-743, 1972 |
|
KEY |
derm, mfd |
|
CLA |
unknown, basic |
|
LOC |
17 q23-25 |
|
MIM |
MIM: 602723 |
|
SYN |
PSOR |
