Genetic linkage of the keratin type II gene cluster with ichthyosis bullosa of Siemens and with autosomal dominant ichthyosis exfoliativa.

Ichthyosis bullosa of Siemens is an autosomal dominant disease characterized by mild hyperkeratosis and blistering. Autosomal dominant ichthyosis exfoliativa is a recently described disease with clinical features similar to ichthyosis bullosa of Siemens, but in contrast to ichthyosis bullosa of Siemens no histologic signs typical for epidermolytic hyperkeratosis are observed. We used linkage analysis to test whether keratin gene mutations might underlie both diseases. This analysis showed linkage of both disorders with the region of chromosome 12 in which the keratin type II gene cluster is located. The keratin type I gene cluster on chromosome 17 is excluded. These data, combined with clinical observations, strongly suggest that the genes coding for keratin 1 or keratin 2e, both expressed in the suprabasal compartment of the epidermis and located in the type II gene cluster, are candidate genes for ichthyosis bullosa of Siemens and ichthyosis exfoliativa.

[1]  R. Happle,et al.  Ichthyosis bullosa of Siemens: Further delineation of the phenotype , 2004, Archives of Dermatological Research.

[2]  A. Deutman,et al.  Localization of the gene for dominant cystoid macular dystrophy on chromosome 7p. , 1994, Human molecular genetics.

[3]  Karl Sperling,et al.  Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK) , 1994, Nature Genetics.

[4]  J. Compton.  Epidermal disease: faulty keratin filaments take their toll , 1994, Nature Genetics.

[5]  G. Lenoir,et al.  Epidermolytic palmoplantar keratoderma cosegregates with a keratin 9 mutation in a pedigree with breast and ovarian cancer , 1994, Nature Genetics.

[6]  E. Lane,et al.  Mutations in the genes for epidermal keratins in epidermolysis bullosa and epidermolytic hyperkeratosis. , 1993, Archives of dermatology.

[7]  A. Ranki,et al.  Evidence against keratin gene mutations in a family with ichthyosis hystrix Curth-Macklin. , 1993, The Journal of investigative dermatology.

[8]  M. King,et al.  High-density genetic map of the BRCA1 region of chromosome 17q12-q21. , 1993, Genomics.

[9]  D. Mischke,et al.  Allelic variations of human keratins K4 and K5 provide polymorphic markers within the type II keratin gene cluster on chromosome 12. , 1993, The Journal of investigative dermatology.

[10]  A. Letai,et al.  Disease severity correlates with position of keratin point mutations in patients with epidermolysis bullosa simplex. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Steinert,et al.  The two size alleles of human keratin 1 are due to a deletion in the glycine-rich carboxyl-terminal V2 subdomain. , 1992, The Journal of investigative dermatology.

[12]  Elaine Fuchs,et al.  The genetic basis of epidermolytic hyperkeratosis: A disorder of differentiation-specific epidermal keratin genes , 1992, Cell.

[13]  S. Bale,et al.  A leucine→proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis , 1992, Cell.

[14]  S. Kubicka,et al.  Characterization of human cytokeratin 2, an epidermal cytoskeletal protein synthesized late during differentiation. , 1992, Experimental cell research.

[15]  C. Amos,et al.  Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q , 1992, Nature Genetics.

[16]  J. Weber,et al.  Closing in on a breast cancer gene on chromosome 17q. , 1992, American journal of human genetics.

[17]  O. Mcbride,et al.  Extensive size polymorphism of the human keratin 10 chain resides in the C-terminal V2 subdomain due to variable numbers and sizes of glycine loops. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Alana L. Rothman,et al.  Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities. , 1991, Science.

[19]  G. Kolde,et al.  Autosomal dominant ichthyosis exfoliativa , 1991, The British journal of dermatology.

[20]  J. Weber,et al.  Dinucleotide repeat polymorphism at the D15S87 locus. , 1990, Nucleic acids research.

[21]  G. I. Bell,et al.  Human collagen, type II, alpha 1, (COL2A1) gene: VNTR polymorphism detected by gene amplification. , 1990, Nucleic acids research.

[22]  M. Murdoch,et al.  Ichthyosis bullosa of Siemens and bullous ichthyosiform erythroderma–variants of the same disease? , 1990, Clinical and experimental dermatology.

[23]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[24]  R. Happle,et al.  Ichthyosis bullosa of Siemens: a unique type of epidermolytic hyperkeratosis. , 1986, Journal of the American Academy of Dermatology.

[25]  G. Lathrop,et al.  Easy calculations of lod scores and genetic risks on small computers. , 1984, American journal of human genetics.