title: Ehlers-Danlos syndrome with severe early-onset periodontal disease (EDS-VIII) is a distinct, heterogeneous disorder with one predisposition gene at chromosome 12p13.
abstract: 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.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Brooks-Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom. nazneen@icr.ac.uk
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.forename: Melanie
authors.initials: M
authors.lastname: Dunstan
authors.forename: M Dawn
authors.initials: MD
authors.lastname: Teare
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanks
authors.forename: Jenny
authors.initials: J
authors.lastname: Douglas
authors.forename: Kim
authors.initials: K
authors.lastname: Coleman
authors.forename: William E
authors.initials: WE
authors.lastname: Bottomly
authors.forename: Mary E
authors.initials: ME
authors.lastname: Campbell
authors.forename: Britta
authors.initials: B
authors.lastname: Berglund
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Bengt
authors.initials: B
authors.lastname: Forssell
authors.forename: Nigel
authors.initials: N
authors.lastname: Burrows
authors.forename: Peter
authors.initials: P
authors.lastname: Lunt
authors.forename: Ian
authors.initials: I
authors.lastname: Young
authors.forename: Nigel
authors.initials: N
authors.lastname: Williams
authors.forename: Graham R
authors.initials: GR
authors.lastname: Bignell
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: F Michael
authors.initials: FM
authors.lastname: Pope
mesh_terms: 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*
chemical_list: D005819:Genetic Markers