A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2.
Hum Mol Genet
; 7(7): 1143-8, 1998 Jul.
Article
en En
| MEDLINE
| ID: mdl-9618173
Type I and type II keratins form the heteropolymeric intermediate filament cytoskeleton, which is the main stress-bearing structure within epithelial cells. Pachyonychia congenita (PC) is a group of autosomal dominant disorders whose most prominent phenotype is hypertrophic nail dystrophy accompanied by other features of ectodermal dysplasia. It has been shown previously that mutations in either K16 or K6a, which form a keratin expression pair, produce the PC-1 variant (MIM 184510). Mutations in K17 alone, an unpaired accessory keratin, result in the PC-2 phenotype (MIM 184500). Here, we describe a family with PC-2 in which the K17 locus on 17q was excluded and linkage to the type II keratin locus on 12q was obtained (Z max 3.31 at straight theta = 0). Mutation analysis of candidate keratins revealed the first reported missense mutation in K6b, implying that this keratin is the previously unknown expression partner of K17, analogous to the K6a/K16 pair. Co-expression of these genes was confirmed by in situ hybridization and immunohistochemical staining. These results reveal the hitherto unknown role of the K6b isoform in epithelial biology, as well as genetic heterogeneity in PC-2.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de la Piel
/
Mutación Missense
/
Queratinas
/
Enfermedades de la Uña
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido