PMID- 10332028
OWN - NLM
STAT- MEDLINE
DCOM- 19990708
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 6
DP  - 1999 Jun
TI  - N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin
      disease striate palmoplantar keratoderma.
PG  - 971-6
AB  - The N-terminal extracellular domain of the cadherins, calcium-dependent cell
      adhesion molecules, has been shown by X-ray crystallography to be involved in two
      types of interaction: lateral strand dimers and adhesive dimers. Here we describe
      the first human mutation in a cadherin present in desmosome cell junctions that
      removes a portion of this highly conserved first extracellular domain. The
      mutation, in the DSG1 gene coding for a desmoglein (Dsg1), results in the
      deletion of the first and much of the second beta-strand of the first cadherin
      repeat and part of the first Ca2+-binding site, and would be expected to
      compromise strand dimer formation. It causes a dominantly inherited skin disease,
      striate palmoplantar keratoderma (SPPK), mapping to chromosome 18q12.1, in which 
      affected individuals have marked hyperkeratotic bands on the palms and soles. In 
      a three generation Dutch family with SPPK, we have found a G-->A transition in
      the 3" splice acceptor site of intron 2 of the DSG1 gene which segregated with
      the disease phenotype. This causes aberrant splicing of exon 2 to exon 4, which
      are in-frame, with the consequent removal of exon 3 encoding part of the
      prosequence, the mature protein cleavage site and part of the first extracellular
      domain. This mutation emphasizes the importance of this part of the molecule for 
      cadherin function, and of the Dsg1 protein and hence desmosomes in epidermal
      function.
FAU - Rickman, L
AU  - Rickman L
AD  - Division of Membrane Biology, National Institute for Medical Research, The
      Ridgeway, Mill Hill, London, UK.
FAU - Simrak, D
AU  - Simrak D
FAU - Stevens, H P
AU  - Stevens HP
FAU - Hunt, D M
AU  - Hunt DM
FAU - King, I A
AU  - King IA
FAU - Bryant, S P
AU  - Bryant SP
FAU - Eady, R A
AU  - Eady RA
FAU - Leigh, I M
AU  - Leigh IM
FAU - Arnemann, J
AU  - Arnemann J
FAU - Magee, A I
AU  - Magee AI
FAU - Kelsell, D P
AU  - Kelsell DP
FAU - Buxton, R S
AU  - Buxton RS
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Cadherins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DSG1 protein, human)
RN  - 0 (Desmoglein 1)
RN  - 0 (Desmogleins)
RN  - 0 (Desmoplakins)
RN  - 0 (RNA, Messenger)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Cadherins/*genetics
MH  - Cytoskeletal Proteins/genetics
MH  - DNA/chemistry/genetics
MH  - DNA Mutational Analysis
MH  - Desmoglein 1
MH  - Desmogleins
MH  - Desmoplakins
MH  - Desmosomes/chemistry
MH  - Exons/genetics
MH  - Family Health
MH  - Female
MH  - Foot Dermatoses/genetics/pathology
MH  - *Genes, Dominant
MH  - Genetic Linkage
MH  - Humans
MH  - Keratoderma, Palmoplantar/*genetics/pathology
MH  - Male
MH  - Molecular Sequence Data
MH  - Pedigree
MH  - Point Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - RNA Splicing/genetics
MH  - RNA, Messenger/genetics
MH  - Sequence Deletion
MH  - Skin/*metabolism/pathology
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - ddc116 [pii]
AID - 10.1093/hmg/8.6.971 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Jun;8(6):971-6. doi: 10.1093/hmg/8.6.971.