Ehlers-Danlos syndrome with severe early-onset periodontal disease (EDS-VIII) is a distinct, heterogeneous disorder with one predisposition gene at chromosome 12p13.
Ehlers-Danlos VIII (EDS-VIII) is an autosomal dominant disorder characterized by severe early-onset periodontal disease in conjunction with the features of Ehlers-Danlos syndrome (EDS). We performed a genomewide linkage search in a large Swedish pedigree with EDS-VIII and established linkage to a 7-cM interval on chromosome 12p13, generating a maximum multipoint LOD score of 5.17. Analysis of four further pedigrees with EDS-VIII revealed two consistent with linkage to 12p13 and two in which linkage could be excluded, indicating that EDS-VIII is a genetically heterogeneous disorder. Chromosome 12p13 has not previously been implicated in either EDS or periodontal disease and contains no known collagen genes or collagen-processing enzymes. Mutational screening of the microfibril-associated glycoprotein-2 gene, a strong candidate within the minimal interval, did not reveal any likely pathogenic mutations.
Rahman
Nazneen
N
Section of Cancer Genetics, Institute of Cancer Research, Brooks-Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom. nazneen@icr.ac.uk
Dunstan
Melanie
M
Teare
M Dawn
MD
Hanks
Sandra
S
Douglas
Jenny
J
Coleman
Kim
K
Bottomly
William E
WE
Campbell
Mary E
ME
Berglund
Britta
B
Nordenskjöld
Magnus
M
Forssell
Bengt
B
Burrows
Nigel
N
Lunt
Peter
P
Young
Ian
I
Williams
Nigel
N
Bignell
Graham R
GR
Futreal
P Andrew
PA
Pope
F Michael
FM
D017668:Age of Onset; D002881:Chromosomes, Human, Pair 12; D004535:Ehlers-Danlos Syndrome / Q000150:complications / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010510:Periodontal Diseases / Q000150:complications / Q000235:genetics*
D005819:Genetic Markers