Ichthyosis vulgaris: The filaggrin mutation disease

British Journal of Dermatology

Volumn 168, Issue 6, 2013, Pages 1155-1166

  Thyssen, J P ^a,b   Godoy Gijon, E ^a,c   Elias, P M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c HOSPITAL DE CABUEÑES   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

EMOLLIENT AGENT; FILAGGRIN;

ALLELE; ATOPY; DISEASE COURSE; ELECTRON MICROSCOPY; GENOTYPE ENVIRONMENT INTERACTION; HETEROZYGOTE ADVANTAGE; HUMAN; ICHTHYOSIS VULGARIS; IMMUNOFLUORESCENCE; KERATOSIS; LOSS OF FUNCTION MUTATION; META ANALYSIS (TOPIC); PHENOTYPIC VARIATION; PRIORITY JOURNAL; REVIEW; SKIN FISSURE; XEROSIS;

ANIMALS; CATS; HUMANS; ICHTHYOSIS VULGARIS; INTERMEDIATE FILAMENT PROTEINS; MUTATION; RISK FACTORS;

EID: 84878656041     PISSN: 00070963     EISSN: 13652133     Source Type: Journal    
DOI: 10.1111/bjd.12219     Document Type: Review

References (124)

1. Wells RS,. Ichthyosis. Br Med J 1966; 2: 1504-6.
2. Elias PM, Williams ML, Crumrine D, Schmuth M,. Inherited disorders of corneocyte proteins. In: Ichthyoses: Clinical, Biochemical, Pathogenic and Diagnostic Assessment (, Elias PM, Williams ML, Crumrine D, Schmuth M, eds). Basel: Karger, 2010; 98-131.
3. Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol 2010; 63: 607-41.
4. Fleckman P, Holbrook KA, Dale BA, et al. Keratinocytes cultured from subjects with ichthyosis vulgaris are phenotypically abnormal. J Invest Dermatol 1987; 88: 640-5.
5. Sybert VP, Dale BA, Holbrook KA,. Ichthyosis vulgaris: identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules. J Invest Dermatol 1985; 84: 191-4.
6. Feinstein A, Ackerman AB, Ziprkowski L,. Histology of autosomal dominant ichthyosis vulgaris and X-linked ichthyosis. Arch Dermatol 1970; 101: 524-7.
7. Presland RB,. Function of filaggrin and caspase-14 in formation and maintenance of the epithelial barrier function. Dermatol Sin 2009; 27: 1-14.
8. Smith FJ, Irvine AD, Terron-Kwiatkowski A, et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006; 38: 337-42.
9. Irvine AD, McLean WH, Leung DY,. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2011; 365: 1315-27.
10. Palmer CN, Irvine AD, Terron-Kwiatkowski A, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006; 38: 441-6.
11. Winge MC, Bilcha KD, Lieden A, et al. Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis. Br J Dermatol 2011; 165: 1074-80.
12. Compton JG, DiGiovanna JJ, Johnston KA, et al. Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1. Exp Dermatol 2002; 11: 518-26.
13. Zhong W, Cui B, Zhang Y, et al. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22. J Hum Genet 2003; 48: 390-2.
14. Sandilands A, O'Regan GM, Liao H, et al. Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis. J Invest Dermatol 2006; 126: 1770-5.
15. Oji V, Seller N, Sandilands A, et al. Ichthyosis vulgaris: novel FLG mutations in the German population and high presence of CD1a+ cells in the epidermis of the atopic subgroup. Br J Dermatol 2009; 160: 771-81.
16. Gruber R, Janecke AR, Fauth C, et al. Filaggrin mutations p.R501X and c.2282del4 in ichthyosis vulgaris. Eur J Hum Genet 2007; 15: 179-84.
17. Sandilands A, Terron-Kwiatkowski A, Hull PR, et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 2007; 39: 650-4.
18. Liu P, Yang Q, Wang X, et al. Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2. J Invest Dermatol 2008; 128: 1418-22.
19. Zhang H, Guo Y, Wang W, et al. Associations of FLG mutations between ichthyosis vulgaris and atopic dermatitis in Han Chinese. Allergy 2011; 66: 1253-4.
20. Nomura T, Akiyama M, Sandilands A, et al. Prevalent and rare mutations in the gene encoding filaggrin in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Invest Dermatol 2009; 129: 1302-5.
21. Sinclair C, O'Toole EA, Paige D, et al. Filaggrin mutations are associated with ichthyosis vulgaris in the Bangladeshi population. Br J Dermatol 2009; 160: 1113-15.
22. Zhang X, Liu S, Chen X, et al. Novel and recurrent mutations in the filaggrin gene in Chinese patients with ichthyosis vulgaris. Br J Dermatol 2010; 163: 63-9.
23. Nomura T, Sandilands A, Akiyama M, et al. Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Allergy Clin Immunol 2007; 119: 434-40.
24. Chen H, Ho JC, Sandilands A, et al. Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris. J Invest Dermatol 2008; 128: 1669-75.
25. Hsu CK, Akiyama M, Nemoto-Hasebe I, et al. Analysis of Taiwanese ichthyosis vulgaris families further demonstrates differences in FLG mutations between European and Asian populations. Br J Dermatol 2009; 161: 448-51.
26. Droitcourt C, Touboul D, Ged C, et al. A prospective study of filaggrin null mutations in keratoconus patients with or without atopic disorders. Dermatology 2011; 222: 336-41.
27. Mlitz V, Latreille J, Gardinier S, et al. Impact of filaggrin mutations on Raman spectra and biophysical properties of the stratum corneum in mild to moderate atopic dermatitis. J Eur Acad Dermatol Venereol 2012; 26: 983-90.
28. Giardina E, Paolillo N, Sinibaldi C, et al. R501X and 2282del4 filaggrin mutations do not confer susceptibility to psoriasis and atopic dermatitis in Italian patients. Dermatology 2008; 216: 83-4.
29. Cascella R, Foti Cuzzola V, Lepre T, et al. Full sequencing of the FLG gene in Italian patients with atopic eczema: evidence of new mutations, but lack of an association. J Invest Dermatol 2011; 131: 982-4.
30. Brown SJ, McLean WH,. One remarkable molecule: filaggrin. J Invest Dermatol 2012; 132: 751-62.
31. Lee DE, Park SY, Han JY, et al. Association between filaggrin mutations and atopic dermatitis in Korean pregnant women. Int J Dermatol 2011. doi: 10.1111/j.1365-4632.2011.05062.x. (Epub ahead of print).
32. Candi E, Schmidt R, Melino G,. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 2005; 6: 328-40.
33. Scott IR, Harding CR,. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol 1986; 115: 84-92.
34. Gibbs NK, Norval M,. Urocanic acid in the skin: a mixed blessing? J Invest Dermatol 2011; 131: 14-17.
35. Gruber R, Elias PM, Crumrine D, et al. Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function. Am J Pathol 2011; 178: 2252-63.
36. Angelova-Fischer I, Mannheimer AC, Hinder A, et al. Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling. Exp Dermatol 2011; 20: 351-6.
37. Jungersted JM, Scheer H, Mempel M, et al. Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema. Allergy 2010; 65: 911-18.
38. Scott IR,. Alterations in the metabolism of filaggrin in the skin after chemical- and ultraviolet-induced erythema. J Invest Dermatol 1986; 87: 460-5.
39. Ramesh R, Chen H, Kukula A, et al. Exacerbation of X-linked ichthyosis phenotype in a female by inheritance of filaggrin and steroid sulfatase mutations. J Dermatol Sci 2011; 64: 159-62.
40. Kezic S, Kemperman PM, Koster ES, et al. Loss-of-function mutations in the filaggrin gene lead to reduced level of natural moisturizing factor in the stratum corneum. J Invest Dermatol 2008; 128: 2117-19.
41. Kezic S, Kammeyer A, Calkoen F, et al. Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods. Br J Dermatol 2009; 161: 1098-104.
42. Mildner M, Jin J, Eckhart L, et al. Knockdown of filaggrin impairs diffusion barrier function and increases UV sensitivity in a human skin model. J Invest Dermatol 2010; 130: 2286-94.
43. Jensen AO, Svaerke C, Kormendine FD, et al. Atopic dermatitis and risk of skin cancer: a Danish nationwide cohort study (1977-2006). Am J Clin Dermatol 2012; 13: 29-36.
44. Thyssen JP, Thuesen BH, Huth C, et al. Skin barrier abnormality due to FLG mutations is associated with increased serum vitamin D concentrations. J Allergy Clin Immunol 2012; 130: 1204-7.
45. Scharschmidt TC, Man MQ, Hatano Y, et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol 2009; 124: 496-506.
46. Fallon PG, Sasaki T, Sandilands A, et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet 2009; 41: 602-8.
47. Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol 2006; 118: 214-19.
48. Thyssen JP, Johansen JD, Linneberg A, et al. The association between null mutations in the filaggrin gene and contact sensitization to nickel and other chemicals in the general population. Br J Dermatol 2010; 162: 1278-85.
49. Kimber I, Dearman RJ,. An assessment of the ability of phthalates to influence immune and allergic responses. Toxicology 2010; 271: 73-82.
50. Bisgaard H, Simpson A, Palmer CN, et al. Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Med 2008; 5: e131.
51. Schuttelaar ML, Kerkhof M, Jonkman MF, et al. Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure. Allergy 2009; 64: 1758-65.
52. Berg ND, Husemoen LL, Thuesen BH, et al. Interaction between filaggrin null mutations and tobacco smoking in relation to asthma. J Allergy Clin Immunol 2012; 129: 374-80.
53. Henderson J, Northstone K, Lee SP, et al. The burden of disease associated with filaggrin mutations: a population-based, longitudinal birth cohort study. J Allergy Clin Immunol 2008; 121: 872-7.
54. Thyssen JP, Linneberg A, Johansen JD, et al. Atopic diseases by filaggrin mutations and birth year. Allergy 2012; 67: 705-8.
55. Brown SJ, Relton CL, Liao H, et al. Filaggrin null mutations and childhood atopic eczema: a population-based case-control study. J Allergy Clin Immunol 2008; 121: 940-6.
56. Thyssen JP, Carlsen BC, Bisgaard H, et al. Individuals who are homozygous for the 2282del4 and R501X filaggrin null mutations do not always develop dermatitis and complete long-term remission is possible. J Eur Acad Dermatol Venereol 2012; 26: 386-9.
57. Chen H, Common JE, Haines RL, et al. Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations. Br J Dermatol 2011; 165: 106-14.
58. Ziprkowski L, Feinstein A,. A survey of ichthyosis vulgaris in Israel. Br J Dermatol 1972; 86: 1-8.
59. Wells RS, Kerr CB,. Clinical features of autosomal dominant and sex-linked ichthyosis in an English population. Br Med J 1966; 1: 947-50.
60. Kuokkanen K,. Ichthyosis vulgaris. A clinical and histopathological study of patients and their close relatives in the autosomal dominant and sex-linked forms of the disease. Acta Derm Venereol Suppl (Stockh) 1969; 62: 1-72.
61. Wells RS, Kerr CB,. Genetic classification of ichthyosis. Arch Dermatol 1965; 92: 1-6.
62. Sergeant A, Campbell LE, Hull PR, et al. Heterozygous null alleles in filaggrin contribute to clinical dry skin in young adults and the elderly. J Invest Dermatol 2009; 129: 1042-5.
63. Novak N, Baurecht H, Schafer T, et al. Loss-of-function mutations in the filaggrin gene and allergic contact sensitization to nickel. J Invest Dermatol 2008; 128: 1430-5.
64. Rice NE, Patel BD, Lang IA, et al. Filaggrin gene mutations are associated with asthma and eczema in later life. J Allergy Clin Immunol 2008; 122: 834-6.
65. Thyssen JP, Ross-Hansen K, Johansen JD, et al. Filaggrin loss-of-function mutation R501X and 2282del4 carrier status is associated with fissured skin on the hands: results from a cross-sectional population study. Br J Dermatol 2011; 166: 46-53.
66. Thyssen JP, Menné T, Zachariae C,. [Minerva-no title]. BMJ 2012; 344: e2441.
67. Brown SJ, Relton CL, Liao H, et al. Filaggrin haploinsufficiency is highly penetrant and is associated with increased severity of eczema: further delineation of the skin phenotype in a prospective epidemiological study of 792 school children. Br J Dermatol 2009; 161: 884-9.
68. Oji V, Traupe H,. Ichthyosis: clinical manifestations and practical treatment options. Am J Clin Dermatol 2009; 10: 351-64.
69. Fleckman P, Brumbaugh S,. Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris. Exp Dermatol 2002; 11: 327-36.
70. Frost P, Van Scott EJ,. Ichthyosiform dermatoses. Classification based on anatomic and biometric observations. Arch Dermatol 1966; 94: 113-26.
71. van den Oord RA, Sheikh A,. Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis. BMJ 2009; 339: b2433.
72. Rodriguez E, Baurecht H, Herberich E, et al. Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol 2009; 123: 1361-70.
73. Weidinger S, Rodriguez E, Stahl C, et al. Filaggrin mutations strongly predispose to early-onset and extrinsic atopic dermatitis. J Invest Dermatol 2007; 127: 724-6.
74. Barker JN, Palmer CN, Zhao Y, et al. Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood. J Invest Dermatol 2007; 127: 564-7.
75. Stemmler S, Parwez Q, Petrasch-Parwez E, et al. Two common loss-of-function mutations within the filaggrin gene predispose for early onset of atopic dermatitis. J Invest Dermatol 2007; 127: 722-4.
76. Flohr C, England K, Radulovic S, et al. Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age. Br J Dermatol 2010; 163: 1333-6.
77. Zhang H, Guo Y, Wang W, et al. Mutations in the filaggrin gene in Han Chinese patients with atopic dermatitis. Allergy 2011; 66: 420-7.
78. Brown SJ, Sandilands A, Zhao Y, et al. Prevalent and low-frequency null mutations in the filaggrin gene are associated with early-onset and persistent atopic eczema. J Invest Dermatol 2008; 128: 1591-4.
79. Imoto Y, Enomoto H, Fujieda S, et al. S2554X mutation in the filaggrin gene is associated with allergen sensitization in the Japanese population. J Allergy Clin Immunol 2010; 125: 498-500.
80. Li M, Liu Q, Liu J, et al. Mutations analysis in filaggrin gene in northern China patients with atopic dermatitis. J Eur Acad Dermatol Venereol 2013; 27: 169-74.
81. Brown SJ, Asai Y, Cordell HJ, et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 2011; 127: 661-7.
82. Weidinger S, O'Sullivan M, Illig T, et al. Filaggrin mutations, atopic eczema, hay fever, and asthma in children. J Allergy Clin Immunol 2008; 121: 1203-9.
83. Marenholz I, Kerscher T, Bauerfeind A, et al. An interaction between filaggrin mutations and early food sensitization improves the prediction of childhood asthma. J Allergy Clin Immunol 2009; 123: 911-16.
84. Li M, Chen X, Chen R, et al. Filaggrin gene mutations are associated with independent atopic asthma in Chinese patients. Allergy 2011; 66: 1616-17.
85. Poninska J, Samolinski B, Tomaszewska A, et al. Filaggrin gene defects are independent risk factors for atopic asthma in a Polish population: a study in ECAP cohort. PLoS ONE 2011; 6: e16933.
86. Muller S, Marenholz I, Lee YA, et al. Association of filaggrin loss-of-function-mutations with atopic dermatitis and asthma in the Early Treatment of the Atopic Child (ETAC) population. Pediatr Allergy Immunol 2009; 20: 358-61.
87. Cookson WO, Ubhi B, Lawrence R, et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet 2001; 27: 372-3.
88. Capon F, Novelli G, Semprini S, et al. Searching for psoriasis susceptibility genes in Italy: genome scan and evidence for a new locus on chromosome 1. J Invest Dermatol 1999; 112: 32-5.
89. Hu Z, Xiong Z, Xu X, et al. Loss-of-function mutations in filaggrin gene associate with psoriasis vulgaris in Chinese population. Hum Genet 2012; 131: 1269-74.
90. Thyssen J, Johansen J, Carlsen B, et al. The filaggrin null genotypes R501X and 2282del4 seem not to be associated with psoriasis: results from general population study and meta-analysis. J Eur Acad Dermatol Venereol 2012; 26: 782-4.
91. Hüffmeier U, Traupe H, Oji V, et al. Loss-of-function variants of the filaggrin gene are not major susceptibility factors for psoriasis vulgaris or psoriatic arthritis in German patients. J Invest Dermatol 2007; 127: 1367-70.
92. Chang YC, Wu WM, Chen CH, et al. Association between P478S polymorphism of the filaggrin gene and risk of psoriasis in a Chinese population in Taiwan. Arch Dermatol Res 2008; 300: 133-7.
93. Weichenthal M, Ruether A, Schreiber S, et al. Filaggrin R501X and 2282del4 mutations are not associated with chronic plaque-type psoriasis in a German cohort. J Invest Dermatol 2007; 127: 1535-7.
94. Zhao Y, Terron-Kwiatkowski A, Liao H, et al. Filaggrin null alleles are not associated with psoriasis. J Invest Dermatol 2007; 127: 1878-82.
95. Winge MC, Suneson J, Lysell J, et al. Lack of association between filaggrin gene mutations and onset of psoriasis in childhood. J Eur Acad Dermatol Venereol 2013; 27: e124-7.
96. Betz RC, Pforr J, Flaquer A, et al. Loss-of-function mutations in the filaggrin gene and alopecia areata: strong risk factor for a severe course of disease in patients comorbid for atopic disease. J Invest Dermatol 2007; 127: 2539-43.
97. Cai SC, Chen H, Koh WP, et al. Filaggrin mutations are associated with recurrent skin infection in Singaporean Chinese patients with atopic dermatitis. Br J Dermatol 2012; 166: 200-3.
98. Gao PS, Rafaels NM, Hand T, et al. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. J Allergy Clin Immunol 2009; 124: 507-13.
99. Thyssen JP, Carlsen BC, Menne T, et al. Filaggrin null mutations increase the risk and persistence of hand eczema in subjects with atopic dermatitis: results from a general population study. Br J Dermatol 2010; 163: 115-20.
100. Molin S, Vollmer S, Weiss EH, et al. Filaggrin mutations may confer susceptibility to chronic hand eczema characterized by combined allergic and irritant contact dermatitis. Br J Dermatol 2009; 161: 801-7.
101. Visser MJ, Landeck L, Campbell LE, et al. Impact of loss-of-function mutations in the filaggrin gene and atopic dermatitis on the development of occupational irritant contact dermatitis. Br J Dermatol 2013; 168: 326-32.
102. de Jongh CM, Khrenova L, Verberk MM, et al. Loss-of-function polymorphisms in the filaggrin gene are associated with an increased susceptibility to chronic irritant contact dermatitis: a case-control study. Br J Dermatol 2008; 159: 621-7.
103. Carlsen BC, Johansen JD, Menné T, et al. Filaggrin null mutations and association with contact allergy and allergic contact dermatitis: results from a tertiary dermatology clinic. Contact Dermatitis 2010; 63: 89-95.
104. Thyssen JP, Linneberg A, Ross-Hansen K, et al. Filaggrin mutations are strongly associated with contact sensitization in individuals with dermatitis. Contact Dermatitis 2013. doi: 10.1111/cod.12021.
105. Thyssen JP, Carlsen BC, Johansen JD, et al. Filaggrin null-mutations may be associated with a distinct subtype of atopic hand eczema. Acta Derm Venereol 2010; 90: 528.
106. Carson CG, Rasmussen MA, Thyssen JP, et al. Clinical presentation of atopic dermatitis by filaggrin gene mutation status during the first 7 years of life in a prospective cohort study. PLoS ONE 2012; 7: e48678.
107. Ross-Hansen K, Menné T, Johansen JD, et al. Nickel reactivity and filaggrin null mutations-evaluation of the filaggrin bypass theory in a general population. Contact Dermatitis 2011; 64: 24-31.
108. Thyssen JP, Linneberg A, Carlsen BC, et al. A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study. BMJ Open 2011; 1: e000062.
109. Vahlquist A, Ganemo A, Virtanen M,. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol 2008; 88: 4-14.
110. Simpson EL, Berry TM, Brown PA, et al. A pilot study of emollient therapy for the primary prevention of atopic dermatitis. J Am Acad Dermatol 2010; 63: 587-93.
111. Gruber R, Janecke AR, Grabher D, et al. Lower prevalence of common filaggrin mutations in a community sample of atopic eczema: is disease severity important? Wien Klin Wochenschr 2010; 122: 551-7.
112. Greisenegger E, Novak N, Maintz L, et al. Analysis of four prevalent filaggrin mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis. J Eur Acad Dermatol Venereol 2010; 24: 607-10.
113. Cramer C, Link E, Horster M, et al. Elder siblings enhance the effect of filaggrin mutations on childhood eczema: results from the 2 birth cohort studies LISAplus and GINIplus. J Allergy Clin Immunol 2010; 125: 1254-60.
114. Van Limbergen J, Russell RK, Nimmo ER, et al. Filaggrin loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2009; 15: 1492-8.
115. Ma L, Zhang L, Di ZH, et al. Association analysis of filaggrin gene mutations and atopic dermatitis in Northern China. Br J Dermatol 2010; 162: 225-7.
116. Nomura T, Akiyama M, Sandilands A, et al. Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan. J Invest Dermatol 2008; 128: 1436-41.
117. Nemoto-Hasebe I, Akiyama M, Nomura T, et al. FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema. Br J Dermatol 2009; 161: 1387-90.
118. Common JE, Brown SJ, Haines RL, et al. Filaggrin null mutations are not a protective factor for acne vulgaris. J Invest Dermatol 2011; 131: 1378-80.
119. Ching GK, Hon KL, Ng PC, et al. Filaggrin null mutations in childhood atopic dermatitis among the Chinese. Int J Immunogenet 2009; 36: 251-4.
120. Wang IJ, Lin TJ, Kuo CF, et al. Filaggrin polymorphism P478S, IgE level and atopic phenotypes. Br J Dermatol 2011; 164: 791-6.
121. Mevorah B, Marazzi A, Frenk E,. The prevalence of accentuated palmoplantar markings and keratosis pilaris in atopic dermatitis, autosomal dominant ichthyosis and control dermatological patients. Br J Dermatol 1985; 112: 679-85.
122. Uehara M, Hayashi S,. Hyperlinear palms: association with ichthyosis and atopic dermatitis. Arch Dermatol 1981; 117: 490-1.
123. Ruether A, Stoll M, Schwarz T, et al. Filaggrin loss-of-function variant contributes to atopic dermatitis risk in the population of Northern Germany. Br J Dermatol 2006; 155: 1093-4.
124. Rodriguez S, Hall AJ, Granell R, et al. Carrier status for the common R501X and 2282del4 filaggrin mutations is not associated with hearing phenotypes in 5,377 children from the ALSPAC cohort. PLoS ONE 2009; 4: e5784.