Striate palmoplantar keratoderma (SPPK; OMIM #148700) is a rare autosomal dominant genodermatosis characterized by linear hyperkeratosis on the digits and hyperkeratosis on the palms and soles. SPPK is known to be caused by heterozygous mutations in either the desmoglein 1 (DSG1), desmoplakin (DSP), or keratin 1 (KRT1) genes.
To define the molecular basis of SPPK in five Pakistani families showing a clear autosomal dominant inheritance pattern of SPPK.
Based on previous reports of DSG1 mutations in SPPK, we performed direct sequencing of the DSG1 gene of all five families.
Mutation analysis resulted in the identification of one recurrent mutation (p.R26X) and four novel mutations (c.Ivs4-2A>G, c.515C>T, c.Ivs9-3C>G, and c.1399delA) in the DSG1 gene. Each mutation is predicted to cause haploinsufficiency of DSG1 protein.
The results of our study further underscore the significance of the desmoglein gene family in diseases of epidermal integrity.
Abbreviations:SPPK (striate palmoplantar keratoderma), PTC (premature termination codon)
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Dermatological Science
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Striate palmoplantar keratoderma.Dermatol Online J. 2002; 8: 16
- Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma.Eur J Hum Genet. 2001; 9: 197-203
- Inherited disorders of desmosomes.Australas J Dermatol. 2005; 46: 221-229
- Desmosomes from a structural perspective.Curr Opin Cell Biol. 2007; 5: 565-571
- The molecular architecture of cadherins in native epidermal desmosomes.Nature. 2007; 7171: 832-837
- Getting under the skin of epidermal morphogenesis.Nat Rev Genet. 2002; 3: 199-209
- N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma.Hum Mol Genet. 1999; 8: 971-976
- Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma.Hum Mol Genet. 1999; 8: 143-148
- Striate palmoplantar keratoderma resulting from desmoplakin haploinsufficiency.J Invest Dermatol. 1999; 113: 940-946
- Frameshift mutation in the V2 domain of human Keratin 1 results in striate palmoplantar keratoderma.J Invest Dermatol. 2002; 118: 838-844
- Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, wooly hair and keratoderma.Hum Mol Genet. 2000; 9: 2761-2766
- Early death from cardiomyopathy in a family with autosomal dominant striate palmoplantar keratoderma and woolly hair associated with a novel insertion mutation in desmoplakin.J Invest Dermatol. 2006; 126: 1651-1654
- A nonsense mutation in the desmoglein 1 gene underlies striate keratoderma.Exp Dermatol. 2003; 12: 523-527
- Focal palmoplantar keratoderma caused by an autosomal dominant inherited mutation in the desmoglein 1 gene.Dermatology. 2006; 212: 117-122
- Striate palmoplantar keratoderma resulting from a frameshift mutation in the desmoglein 1 gene.J Dermatol Sci. 2007; 45: 161-166
- Characterization of the desmosomal cadherin gene family: genomic organization of two desmoglein genes on human chromosome 18q12.Exp Dermatol. 2001; 10: 90-94
- Cytosine methylation: the pros and cons of DNA methylation.Curr Biol. 1993; 6: 384-386
- Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants.Hum Genet. 2006; 119: 9-22
- Defects in RNA splicing and the consequence of shortened translational reading frames.Am J Hum Genet. 1996; 59: 279-286
- Nonsense-mediated mRNA decay in health and disease.Hum Mol Genet. 1999; 8: 1893-1900
Published online: July 12, 2010
Accepted: November 13, 2008
Received in revised form: November 9, 2008
Received: July 25, 2008
© 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.