title: A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome.
abstract: Terminal keratinocyte differentiation involves coordinated expression of several functionally interdependent genes, many of which have been mapped to the epidermal differentiation complex (EDC) on chromosome 1q21. We have identified linkage of Vohwinkel's syndrome in an extended pedigree to markers flanking the EDC region with a maximum multipoint lod score of 14.3. Sequencing of the loricrin gene revealed an insertion that shifts the translation frame of the C-terminal Gly- and Gln/Lys-rich domains, and is likely to impair cornification. Our findings provide the first evidence for a defect in an EDC gene in human disease, and disclose novel insights into perturbations of cornified cell envelope formation.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
authors.forename: E
authors.initials: E
authors.lastname: Maestrini
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: A
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: C
authors.initials: C
authors.lastname: Camisa
authors.forename: A
authors.initials: A
authors.lastname: Hovnanian
authors.forename: D E
authors.initials: DE
authors.lastname: Weeks
authors.forename: M
authors.initials: M
authors.lastname: Lathrop
authors.forename: J
authors.initials: J
authors.lastname: Uitto
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017931:DNA Primers; D004251:DNA Transposable Elements; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012867:Skin / Q000473:pathology / Q000648:ultrastructure; D013577:Syndrome
chemical_list: D017931:DNA Primers; D004251:DNA Transposable Elements; D005819:Genetic Markers; D008565:Membrane Proteins; C064554:loricrin