Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function.

EL Rugg; SM Morley; FJ Smith; M Boxer; MJ Tidman; H Navsaria; IM Leigh; EB Lane

doi:10.1038/ng1193-294

Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function.

EL Rugg, SM Morley, FJ Smith, M Boxer, MJ Tidman, H Navsaria, IM Leigh, EB Lane

Research output: Contribution to journal › Article › peer-review

87 Citations (Scopus)

Abstract

We have identified mutations in keratins K5 (Arg331Cys) and K14 (Val270Met) in two kinships affected by the dominantly-inherited skin blistering disease, Weber-Cockayne epidermolysis bullosa simplex (EBS-WC). Linkage analysis, DNA sequencing and clinical and ultrastructural analysis are combined to provide the first detailed description of classical EBS-WC. Both phenotypes show similar blistering on trauma, indicating that both mutations compromise the structural resilience of the basal keratinocytes by affecting the keratin cytoskeleton. The location of these mutations in the L12 linker, which bisects the alpha-helical rod region of intermediate filament proteins, identifies another keratin mutation cluster leading to hereditary skin fragility syndromes.

Original language	English
Pages (from-to)	294-300
Number of pages	7
Journal	Nature Genetics
Volume	5
Issue number	3
DOIs	https://doi.org/10.1038/ng1193-294
Publication status	Published - Nov 1993

Keywords

Age of Onset
Amino Acid Sequence
Base Sequence
Cells, Cultured
Child
Child, Preschool
Cytoskeleton
DNA Primers
Epidermolysis Bullosa Simplex
Female
Humans
Infant, Newborn
Keratins
Male
Microscopy, Electron
Molecular Sequence Data
Mutation
Phenotype
Skin

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10.1038/ng1193-294

http://europepmc.org/abstract/MED/7506097

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title = "Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function.",

abstract = "We have identified mutations in keratins K5 (Arg331Cys) and K14 (Val270Met) in two kinships affected by the dominantly-inherited skin blistering disease, Weber-Cockayne epidermolysis bullosa simplex (EBS-WC). Linkage analysis, DNA sequencing and clinical and ultrastructural analysis are combined to provide the first detailed description of classical EBS-WC. Both phenotypes show similar blistering on trauma, indicating that both mutations compromise the structural resilience of the basal keratinocytes by affecting the keratin cytoskeleton. The location of these mutations in the L12 linker, which bisects the alpha-helical rod region of intermediate filament proteins, identifies another keratin mutation cluster leading to hereditary skin fragility syndromes.",

keywords = "Age of Onset, Amino Acid Sequence, Base Sequence, Cells, Cultured, Child, Child, Preschool, Cytoskeleton, DNA Primers, Epidermolysis Bullosa Simplex, Female, Humans, Infant, Newborn, Keratins, Male, Microscopy, Electron, Molecular Sequence Data, Mutation, Phenotype, Skin",

author = "EL Rugg and SM Morley and FJ Smith and M Boxer and MJ Tidman and H Navsaria and IM Leigh and EB Lane",

note = "Research Support, Non-U.S. Gov't,",

year = "1993",

month = nov,

doi = "10.1038/ng1193-294",

language = "English",

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journal = "Nature Genetics",

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T1 - Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function.

AU - Rugg, EL

AU - Morley, SM

AU - Smith, FJ

AU - Boxer, M

AU - Tidman, MJ

AU - Navsaria, H

AU - Leigh, IM

AU - Lane, EB

N1 - Research Support, Non-U.S. Gov't,

PY - 1993/11

Y1 - 1993/11

N2 - We have identified mutations in keratins K5 (Arg331Cys) and K14 (Val270Met) in two kinships affected by the dominantly-inherited skin blistering disease, Weber-Cockayne epidermolysis bullosa simplex (EBS-WC). Linkage analysis, DNA sequencing and clinical and ultrastructural analysis are combined to provide the first detailed description of classical EBS-WC. Both phenotypes show similar blistering on trauma, indicating that both mutations compromise the structural resilience of the basal keratinocytes by affecting the keratin cytoskeleton. The location of these mutations in the L12 linker, which bisects the alpha-helical rod region of intermediate filament proteins, identifies another keratin mutation cluster leading to hereditary skin fragility syndromes.

AB - We have identified mutations in keratins K5 (Arg331Cys) and K14 (Val270Met) in two kinships affected by the dominantly-inherited skin blistering disease, Weber-Cockayne epidermolysis bullosa simplex (EBS-WC). Linkage analysis, DNA sequencing and clinical and ultrastructural analysis are combined to provide the first detailed description of classical EBS-WC. Both phenotypes show similar blistering on trauma, indicating that both mutations compromise the structural resilience of the basal keratinocytes by affecting the keratin cytoskeleton. The location of these mutations in the L12 linker, which bisects the alpha-helical rod region of intermediate filament proteins, identifies another keratin mutation cluster leading to hereditary skin fragility syndromes.

KW - Age of Onset

KW - Amino Acid Sequence

KW - Base Sequence

KW - Cells, Cultured

KW - Child

KW - Child, Preschool

KW - Cytoskeleton

KW - DNA Primers

KW - Epidermolysis Bullosa Simplex

KW - Female

KW - Humans

KW - Infant, Newborn

KW - Keratins

KW - Male

KW - Microscopy, Electron

KW - Molecular Sequence Data

KW - Mutation

KW - Phenotype

KW - Skin

U2 - 10.1038/ng1193-294

DO - 10.1038/ng1193-294

M3 - Article

SN - 1061-4036

VL - 5

SP - 294

EP - 300

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function.

Abstract

Keywords

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