多发性脂囊瘤的KRT17基因突变研究
摘要
研究背景多发性脂囊瘤(steatocystoma multiplex,SM,OMIM:184500)是一种少见的皮肤附属器良性肿瘤,临床特征为多发性半球形肤色或淡黄色皮肤囊性损害,好发于躯干部和四肢近心端,常在青春期或成人早期发病,皮疹数目和大小可随年龄增长而不同程度增加。本病多呈常染色体显性遗传,尽管也有诸多散发病例的报道。目前认为该病主要是由KRT17基因的突变所致,同时KRT17基因也是先天性厚甲症2型(Pachyonychia congenital-2,PC-2)的一个致病基因。角蛋白K17常表达于甲床、毛囊外根鞘、皮脂腺和其它附属器,角蛋白有一个由310个氨基酸残基构成的α-螺旋杆状结构域,该结构域由1A、1B、2A和2B四个片段组成。位于1A螺旋起始和2B螺旋末端的序列是高度保守区,对体内10nm中间丝的装配至关重要。KRT17基因定位于17q12-q21,全长5kb,由8个编码蛋白的外显子组成。迄今为止,国内外学者在不同SM家系中共检测到3种不同的突变,目前尚未发现基因型与表型之间的明确相关性。本研究收集了中国汉族人两个多发性脂囊瘤家系,并通过直接测序的方法对这两个家系的成员进行KRT17基因的突变检测。
目的检测中国汉族人两个多发性脂囊瘤家系的KRT17基因的致病性突变。
方法调查两个中国汉族人多发性脂囊瘤家系情况,收集整理家系资料并采集家系成员血样。提取家系成员和100名正常对照的外周血白细胞基因组DNA,设计覆盖KRT17基因所有外显子编码区的7对引物,采用PCR反应扩增所有外显子编码区及其侧翼序列,通过对PCR扩增产物直接测序进行序列分析。
结果通过对中国汉族人多发性脂囊瘤两家系进行突变检测,检测到一个国外曾经报道过的突变c.281G＞A(p.R94H)和一个国内外在多发性脂囊瘤家系中未见报道的突变c.275 A＞G(p.N92S)。而这两个家系中表型正常个体及100个无关正常对照均不存在这样的突变。
结论本研究证实错义突变c.281G＞A(p.R94H)和c.275 A＞G(p.N92S)是引起中国汉族人多发性脂囊瘤两家系临床症状的致病性突变,而不是正常多态性,为将来该家系的遗传咨询、产前诊断及基因治疗打下了基础。
Background Steatocystoma multiplex is a rare benigh shin appendage tumor characterized by multiple hemispheroid,yellow to skin-colored cystic lesions,which are principally on the trunk and proximal parts of the limbs.The papules can increase in number and size throughout adult life.Onset of the disease tends to occur during adolescence or early adult life.It is thought to be inherited in an autosomal dominant fashion,although many sporadic cases have also been reported.It is demonstrated that steatocystoma multiplex is caused by mutation in KRT17 gene,which is also responsible for Pachyonychia congenital-2.KRT17 is expressed in the nail bed,hair. follicle,sebaceous gland and other epidermal appendages.Each keratin polypeptide possesses a 310-amino acid residueα-helical rod domain that consists of four helical segments named 1A,1B,2A and 2B.The sequences at the beginning of the helix 1A and at the end of the helix 2B are highly conserved and are the most critical for the assembly of the 10-nm intermediate filaments in vivo.KRT17 gene which is 5kb long with 8 exons was mapped to chromosome 17q12-q21.Up to date,there have been 3 germline mutations described in the KRT17 gene in cases of SM,no clear correlation between phenotype and genotypes has been established.In the present study,we have ascertained two Chinese kindreds with steatocystoma multiplex and examined KRT17 gene in these families by direct sequencing.
Objective To identify pathogenic mutations of the KRT17 gene in two Chinese kindreds with steatocystoma multiplex.
Methods We investigated two Chinese families with SM,collected clinical datas and blood samples from them.Genomic DNA was extracted from peripheral blood of members in two families and 100 unrelated normal controls.All the coding exons and their flanking sequences of KRT17 gene were amplified by polymerase chain reaction (PCR).The PCR products were directly sequenced to detect the mutation.
Results One novel KRT17 gene mutation(c.275 A＞G) and one mutation(c.281G＞A) previously described were identified in two Chinese kindreds with steatocystoma multiplex.The two mutations were not found in the healthy members of families and in 100 unrelated control individuals.
Conclusions These two missense mutations(c.275A＞G and c.281G＞A) may be the pathogenic mutations in these two Chinese families,not common polymorphism.This study should be useful for genetic counseling,prenatal diagnosis and gene therapy for the patients.
目的检测中国汉族人两个多发性脂囊瘤家系的KRT17基因的致病性突变。
方法调查两个中国汉族人多发性脂囊瘤家系情况,收集整理家系资料并采集家系成员血样。提取家系成员和100名正常对照的外周血白细胞基因组DNA,设计覆盖KRT17基因所有外显子编码区的7对引物,采用PCR反应扩增所有外显子编码区及其侧翼序列,通过对PCR扩增产物直接测序进行序列分析。
结果通过对中国汉族人多发性脂囊瘤两家系进行突变检测,检测到一个国外曾经报道过的突变c.281G＞A(p.R94H)和一个国内外在多发性脂囊瘤家系中未见报道的突变c.275 A＞G(p.N92S)。而这两个家系中表型正常个体及100个无关正常对照均不存在这样的突变。
结论本研究证实错义突变c.281G＞A(p.R94H)和c.275 A＞G(p.N92S)是引起中国汉族人多发性脂囊瘤两家系临床症状的致病性突变,而不是正常多态性,为将来该家系的遗传咨询、产前诊断及基因治疗打下了基础。
Background Steatocystoma multiplex is a rare benigh shin appendage tumor characterized by multiple hemispheroid,yellow to skin-colored cystic lesions,which are principally on the trunk and proximal parts of the limbs.The papules can increase in number and size throughout adult life.Onset of the disease tends to occur during adolescence or early adult life.It is thought to be inherited in an autosomal dominant fashion,although many sporadic cases have also been reported.It is demonstrated that steatocystoma multiplex is caused by mutation in KRT17 gene,which is also responsible for Pachyonychia congenital-2.KRT17 is expressed in the nail bed,hair. follicle,sebaceous gland and other epidermal appendages.Each keratin polypeptide possesses a 310-amino acid residueα-helical rod domain that consists of four helical segments named 1A,1B,2A and 2B.The sequences at the beginning of the helix 1A and at the end of the helix 2B are highly conserved and are the most critical for the assembly of the 10-nm intermediate filaments in vivo.KRT17 gene which is 5kb long with 8 exons was mapped to chromosome 17q12-q21.Up to date,there have been 3 germline mutations described in the KRT17 gene in cases of SM,no clear correlation between phenotype and genotypes has been established.In the present study,we have ascertained two Chinese kindreds with steatocystoma multiplex and examined KRT17 gene in these families by direct sequencing.
Objective To identify pathogenic mutations of the KRT17 gene in two Chinese kindreds with steatocystoma multiplex.
Methods We investigated two Chinese families with SM,collected clinical datas and blood samples from them.Genomic DNA was extracted from peripheral blood of members in two families and 100 unrelated normal controls.All the coding exons and their flanking sequences of KRT17 gene were amplified by polymerase chain reaction (PCR).The PCR products were directly sequenced to detect the mutation.
Results One novel KRT17 gene mutation(c.275 A＞G) and one mutation(c.281G＞A) previously described were identified in two Chinese kindreds with steatocystoma multiplex.The two mutations were not found in the healthy members of families and in 100 unrelated control individuals.
Conclusions These two missense mutations(c.275A＞G and c.281G＞A) may be the pathogenic mutations in these two Chinese families,not common polymorphism.This study should be useful for genetic counseling,prenatal diagnosis and gene therapy for the patients.
引文
1.Plewig G,Wolff HH,Braun-Falco O.Steatocystoma multiplex:Anatomic reevaluation,electron microscopy,and autoradiography.Arch Dermatol Res 1982;272:363-380.
2.Moritz DL,Silverman RA.Steatocystoma multiplex treated with isotretinoin:a delayed response.Cutis 1988;42:437-439.
3.Magid ML,Wentzell JM,Roenigk HH.Multiple cystic lesions.Steatocystoma multiplex.Arch Dermatol 1990;126:101-104.
4.赵辨主编.临床皮肤病学.第3版.江苏科学技术出版社,2001:1141
5.Troyanovsky SM,Leube RE,Franke WW.Characterization of the human gene encoding cytokeratin 17 and its expression pattern.Eur J Cell Biol 1992;59:127-137.
6.Smith FJ,Corden LD,Rugg EL,et al.Missense mutation in keratin 17 cause either pachyonychia congenital type2 or a phenotype resembling steatocystoma multiplex.J Invest Dematol 1997;108:220-223.
7.Covello SP,Smith FJD,Sillevis Smitt JH,et al.Keratin 17 mutation cause either steatocystoma multiplex or pachyonychia congenital type2.Br J Dermatol 1998;139:475-480.
8.王秀英,史耀周,叶月仙,等.多发性脂囊瘤患者角蛋白17基因突变的研究.中华医学杂志 2001;81:540-543.
9.Mclean WH,Rugg EL,Lunny DP,et al.Keratin 16 and keratin 17 mutations cause pachyonychia congenital.Nat Genet 1995;9:273-276.
10.Troyanovsky SM,Guelstein VI,Tchipysheva TA,Krutovkikh VA,Bannikov GA.Patterns of expression of keratin 17 in human epithelia:dependency on cell position.J Cell Sci 1989;93:419-426.
11.Gorlin RJ,Pindborg JJ,Cohen MM Jr.Syndromes of the Head and Neck.New York:McGraw-Hill,1976.
12.Jadassohn J,Lewandowsky F.Pachyonychia congenita.In:Jacobs Ikonographia Dermatologica.Berlin:Urban and Schwarzenberg,1906;29.
13.Jackson ADM,Lawler SD.Pachyonychia congenita:a report of six cases in one family.Ann Eugen 1951;16:142-146.
14.McLean WHI,Rugg EL,Lunny DP et al.Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 1995; 9:273-278.
15. Bowden PE, Haley JL, Kansky A et al. Mutation of a type II keratin gene(K6a) in pachyonychia congenita. Nat Genet 1995; 10:363-365.
16. Smith FJD, van Jonkman MF, Goor H et al. A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2. Hum Mol Genet 1998; 7: 1143-1148.
17. Rebecca MP, Birgitte L. Phenotypes, genotypes and their contribution to understanding keratin function. Trends Genet 2003; 19: 278-285.
18. Fuchs E, Cleveland DW. A structural scaffolding of intermediate filaments in health and disease. Science,1998, 279:514-519.
19. Smith FJD. The molecular genetics of keratin disorders. Am J Clin Dermatol, .2003,4:347-364.
20. Albers K ,Fuchs E .Expression of mutant keratin cDNAs in epithelial cell reveals possible mechanisms for initiation and assembly intermediate filaments. J Cell Biol, 1989,108: 1477-1493.
21. Hatzfeld M, Weber K. A synthetic peptide representing the consensus sequence motif at the carboxy -terminal end of the rod domain inhibits intermediate filament assembly and disassembles preformed filaments. J Cell Biol, 1992,116:157-166.
22. Cassidy AJ, Lane EB, Irvine AD, McLean WHI: The Human Intermediate Filament Mutation Database,2006: http ://www. intetfil. org
23. Smith FJD, Liao H, Cassidy AJ, et al. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10:21—30.
24. Terrinoni A, Smith FJD, Didona B, et al. Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenital. J Invest Dermatol 2001;117:1391-1396.
25. Smith FJD, Coleman CM, Batoumy NM,et al. Novel keratin 17 mutations in pachyonychia congenita type 2. J Invest Dermatol 2001; 116: 806-808.
26. Xiao SX, Feng YG, Ren XR,et al. A novel mutation in the second half of the keratin 17 1A domain in a large pedigree with delayed-onset parchyonychia congenital type 2. J Invest Dermatol 2004; 122: 892-895.
27. Feng YG, Xiao SX, Ren XR,et al. Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts. Br J Dermatol 2003; 148: 452-455.
28. Hashiguchi T, Yotsumoto S, Shimada H,et al. A novel point mutation in the keratin 17 gene in a Japanese case of pachyonychia congenita type 2. J Invest Dermatol 2002; 118: 545-547.
29. Celebi JT, Tanzi EL, Yao YJ,et al. Idendification of a Germline mutation in keratin 17 in a family with pachyonychia congenita type 2. J Invest Dermatol 1999; 113: 848-850.
30. Fujimoto W, Nakanishi G, Hirakawa S,et al. Pachyonychia congenita type 2: Keratin 17 mutation in a Japanese case. J Am Acad Dermatol 38 (6 Part 1) 1998:1007-1009.
31. Se-Woong OH, Moon Young KIM, Jeong Sun LEE,et al. Keratin 17 mutation in pachyonychia congenital type 2 patient with early onset steatocystoma multiplex and Hutchinson-like tooth deformity. Journal of Dermatology 2006;3:161-164.
32. Uchida T, Inaoki M, Makino E, et al. Identification of a recurrent mutation in keratin 17 in a Japanese family with pachyonychia congenita type 2. J Dermatol Sci. 2005;38(1):60-63.
1.Kaya TI,Ikizoglu G,Kokturk A,et al.A simple surgical technique for the treatment of steatocystoma multiplex.Int J Dermatol 2001;40:785-788.
2.Feng YG,Xiao SX,Ren XR,et al.Keratin 17 mutation in Pachyonychia congenita type2 with early onset sebaceous cysts.Br J Dermatol 2003;148:452-455.
3.Troyanovsky SM,Leube RE,Franke wW.Characterization of the human gene encoding cytokeratin 17 and its expression pattern.Eur J Cell Biol 1992;59:127-137.
4.Smith FJ,Corden LD,Rugg EL,et.al.Missense mutation in keratin 17 cause either pachyonychia congenital type2 or a phenotype resembling steatocystoma multiplex.J Invest Dematol 1997;108:220-223.
5.Covello SP,Smith FJD,Sillevis smitt JH,et al.Keratin 17 mutation cause either steatocystoma multiplex or pachyonychia congenital type2.Br J Dermatol 1998;139:475-480.
6.王秀英,史耀舟,叶月仙,等.多发性脂囊瘤患者角蛋白17基因突变的研究,中华医学杂志,2001:81:540-543.
7.PorterRM,LaneEB.Phenotypes,genotypesandtheircontributiontounderstandingkerati nfunction[J].Trends Genet,2003,19(5):278-285.
8.AlanD.Irvine,MD.Inheriteddefectsinkeratins.Clinicsin dermatology,2005,23:6-14.
9.Plewig G,Wolff HH,Braun-Falco O.Steatocystoma multiplex:anatomic evaluation,electron microscopy and autoradiography.Arch Dermatol Res 1982;272:363-380.
10.Kurokawa I,Nishijima S,Kusumoto K,et al.Cytokeratin expression in steatocystoma multiplex.Br J Dermatol 2002;146:534-536.
11.Tomkova H,Fujimoto W,Arata J.Expression of keratins(K10 and K17)in steatocystoma multiplex,eruptive vellus hair cysts,and epidermoid and trichilemmal cysts.Am J Dermatopathol 1997;19:250-253.
12.Yamada A,Saga K,Jimbow K.Acquired multiple pilosebaceous cysts on the face having the histopathological features of steatocystoma multiplex and eruptive vellus hair cysts.Int J Dermatol 2005;44:861-863.
13.Ahn SK,Chung J,Lee WS,etal.Hybrid cysts showing alternate combination of eruptive vellus hair cyst,steatocystoma multiplex,and epidermoid cyst,and an association among the three conditions.Am J Dermatopathol 1996;18:645-649.
14.Statham BN,Cunliffe WJ.The treatment of steatocystoma multiplex suppurativum with isotretinoin.Br J Dermatol 1984;111:246.
15.Notowitcs A.Treatment of lesions of steatocystoma multiplex and other epidermal cysts by cryosurgery.J Dermatol Surg Oncol 1980;6:98-99.
16.Duzova AN,Senturk GB.Suggestion for the treatment of steatocystoma multiplex located exclusively on the face.Int J dermatol 2004;43:60-62.
17.Krahenbuhl A,Eichmann A,Pfaltz M.CO2 laser therapy for steatocystoma multiplex. Dermatologica 1991; 183:294-296.
18. Rossi R, Cappugi P, Battini M, et al. CO2 laser therapy in a case of steatocystoma multiplex with prominent nodules on the face and neck.. Int J dermatol 2003;42:302-304.
19. Apaydin R, Bilen N, Bayramgurler D, et al. Steatocystoma multiplex suppurativum:oral isotretinoin treatment combined with cryotherapy. Australas J Dermatol 2000;41:98-100.
20. Keefe M, Leppard BJ, Royle G. Successful treatment of steatocystoma multiplex by simple surgery. Br J Dermatol 1992; 127:41-44.
21. Schmook T, Burg G, Hafner J.Surgical peal:mini-incisions for the extraction of steatocystoma multiplex. J Am Acad Dermatol 2001 ;44:1041-1042.
2.Moritz DL,Silverman RA.Steatocystoma multiplex treated with isotretinoin:a delayed response.Cutis 1988;42:437-439.
3.Magid ML,Wentzell JM,Roenigk HH.Multiple cystic lesions.Steatocystoma multiplex.Arch Dermatol 1990;126:101-104.
4.赵辨主编.临床皮肤病学.第3版.江苏科学技术出版社,2001:1141
5.Troyanovsky SM,Leube RE,Franke WW.Characterization of the human gene encoding cytokeratin 17 and its expression pattern.Eur J Cell Biol 1992;59:127-137.
6.Smith FJ,Corden LD,Rugg EL,et al.Missense mutation in keratin 17 cause either pachyonychia congenital type2 or a phenotype resembling steatocystoma multiplex.J Invest Dematol 1997;108:220-223.
7.Covello SP,Smith FJD,Sillevis Smitt JH,et al.Keratin 17 mutation cause either steatocystoma multiplex or pachyonychia congenital type2.Br J Dermatol 1998;139:475-480.
8.王秀英,史耀周,叶月仙,等.多发性脂囊瘤患者角蛋白17基因突变的研究.中华医学杂志 2001;81:540-543.
9.Mclean WH,Rugg EL,Lunny DP,et al.Keratin 16 and keratin 17 mutations cause pachyonychia congenital.Nat Genet 1995;9:273-276.
10.Troyanovsky SM,Guelstein VI,Tchipysheva TA,Krutovkikh VA,Bannikov GA.Patterns of expression of keratin 17 in human epithelia:dependency on cell position.J Cell Sci 1989;93:419-426.
11.Gorlin RJ,Pindborg JJ,Cohen MM Jr.Syndromes of the Head and Neck.New York:McGraw-Hill,1976.
12.Jadassohn J,Lewandowsky F.Pachyonychia congenita.In:Jacobs Ikonographia Dermatologica.Berlin:Urban and Schwarzenberg,1906;29.
13.Jackson ADM,Lawler SD.Pachyonychia congenita:a report of six cases in one family.Ann Eugen 1951;16:142-146.
14.McLean WHI,Rugg EL,Lunny DP et al.Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 1995; 9:273-278.
15. Bowden PE, Haley JL, Kansky A et al. Mutation of a type II keratin gene(K6a) in pachyonychia congenita. Nat Genet 1995; 10:363-365.
16. Smith FJD, van Jonkman MF, Goor H et al. A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2. Hum Mol Genet 1998; 7: 1143-1148.
17. Rebecca MP, Birgitte L. Phenotypes, genotypes and their contribution to understanding keratin function. Trends Genet 2003; 19: 278-285.
18. Fuchs E, Cleveland DW. A structural scaffolding of intermediate filaments in health and disease. Science,1998, 279:514-519.
19. Smith FJD. The molecular genetics of keratin disorders. Am J Clin Dermatol, .2003,4:347-364.
20. Albers K ,Fuchs E .Expression of mutant keratin cDNAs in epithelial cell reveals possible mechanisms for initiation and assembly intermediate filaments. J Cell Biol, 1989,108: 1477-1493.
21. Hatzfeld M, Weber K. A synthetic peptide representing the consensus sequence motif at the carboxy -terminal end of the rod domain inhibits intermediate filament assembly and disassembles preformed filaments. J Cell Biol, 1992,116:157-166.
22. Cassidy AJ, Lane EB, Irvine AD, McLean WHI: The Human Intermediate Filament Mutation Database,2006: http ://www. intetfil. org
23. Smith FJD, Liao H, Cassidy AJ, et al. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10:21—30.
24. Terrinoni A, Smith FJD, Didona B, et al. Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenital. J Invest Dermatol 2001;117:1391-1396.
25. Smith FJD, Coleman CM, Batoumy NM,et al. Novel keratin 17 mutations in pachyonychia congenita type 2. J Invest Dermatol 2001; 116: 806-808.
26. Xiao SX, Feng YG, Ren XR,et al. A novel mutation in the second half of the keratin 17 1A domain in a large pedigree with delayed-onset parchyonychia congenital type 2. J Invest Dermatol 2004; 122: 892-895.
27. Feng YG, Xiao SX, Ren XR,et al. Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts. Br J Dermatol 2003; 148: 452-455.
28. Hashiguchi T, Yotsumoto S, Shimada H,et al. A novel point mutation in the keratin 17 gene in a Japanese case of pachyonychia congenita type 2. J Invest Dermatol 2002; 118: 545-547.
29. Celebi JT, Tanzi EL, Yao YJ,et al. Idendification of a Germline mutation in keratin 17 in a family with pachyonychia congenita type 2. J Invest Dermatol 1999; 113: 848-850.
30. Fujimoto W, Nakanishi G, Hirakawa S,et al. Pachyonychia congenita type 2: Keratin 17 mutation in a Japanese case. J Am Acad Dermatol 38 (6 Part 1) 1998:1007-1009.
31. Se-Woong OH, Moon Young KIM, Jeong Sun LEE,et al. Keratin 17 mutation in pachyonychia congenital type 2 patient with early onset steatocystoma multiplex and Hutchinson-like tooth deformity. Journal of Dermatology 2006;3:161-164.
32. Uchida T, Inaoki M, Makino E, et al. Identification of a recurrent mutation in keratin 17 in a Japanese family with pachyonychia congenita type 2. J Dermatol Sci. 2005;38(1):60-63.
1.Kaya TI,Ikizoglu G,Kokturk A,et al.A simple surgical technique for the treatment of steatocystoma multiplex.Int J Dermatol 2001;40:785-788.
2.Feng YG,Xiao SX,Ren XR,et al.Keratin 17 mutation in Pachyonychia congenita type2 with early onset sebaceous cysts.Br J Dermatol 2003;148:452-455.
3.Troyanovsky SM,Leube RE,Franke wW.Characterization of the human gene encoding cytokeratin 17 and its expression pattern.Eur J Cell Biol 1992;59:127-137.
4.Smith FJ,Corden LD,Rugg EL,et.al.Missense mutation in keratin 17 cause either pachyonychia congenital type2 or a phenotype resembling steatocystoma multiplex.J Invest Dematol 1997;108:220-223.
5.Covello SP,Smith FJD,Sillevis smitt JH,et al.Keratin 17 mutation cause either steatocystoma multiplex or pachyonychia congenital type2.Br J Dermatol 1998;139:475-480.
6.王秀英,史耀舟,叶月仙,等.多发性脂囊瘤患者角蛋白17基因突变的研究,中华医学杂志,2001:81:540-543.
7.PorterRM,LaneEB.Phenotypes,genotypesandtheircontributiontounderstandingkerati nfunction[J].Trends Genet,2003,19(5):278-285.
8.AlanD.Irvine,MD.Inheriteddefectsinkeratins.Clinicsin dermatology,2005,23:6-14.
9.Plewig G,Wolff HH,Braun-Falco O.Steatocystoma multiplex:anatomic evaluation,electron microscopy and autoradiography.Arch Dermatol Res 1982;272:363-380.
10.Kurokawa I,Nishijima S,Kusumoto K,et al.Cytokeratin expression in steatocystoma multiplex.Br J Dermatol 2002;146:534-536.
11.Tomkova H,Fujimoto W,Arata J.Expression of keratins(K10 and K17)in steatocystoma multiplex,eruptive vellus hair cysts,and epidermoid and trichilemmal cysts.Am J Dermatopathol 1997;19:250-253.
12.Yamada A,Saga K,Jimbow K.Acquired multiple pilosebaceous cysts on the face having the histopathological features of steatocystoma multiplex and eruptive vellus hair cysts.Int J Dermatol 2005;44:861-863.
13.Ahn SK,Chung J,Lee WS,etal.Hybrid cysts showing alternate combination of eruptive vellus hair cyst,steatocystoma multiplex,and epidermoid cyst,and an association among the three conditions.Am J Dermatopathol 1996;18:645-649.
14.Statham BN,Cunliffe WJ.The treatment of steatocystoma multiplex suppurativum with isotretinoin.Br J Dermatol 1984;111:246.
15.Notowitcs A.Treatment of lesions of steatocystoma multiplex and other epidermal cysts by cryosurgery.J Dermatol Surg Oncol 1980;6:98-99.
16.Duzova AN,Senturk GB.Suggestion for the treatment of steatocystoma multiplex located exclusively on the face.Int J dermatol 2004;43:60-62.
17.Krahenbuhl A,Eichmann A,Pfaltz M.CO2 laser therapy for steatocystoma multiplex. Dermatologica 1991; 183:294-296.
18. Rossi R, Cappugi P, Battini M, et al. CO2 laser therapy in a case of steatocystoma multiplex with prominent nodules on the face and neck.. Int J dermatol 2003;42:302-304.
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