title: 17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD).
abstract: Split-hand/foot malformation with long-bone deficiency (SHFLD) is a relatively rare autosomal-dominant skeletal disorder, characterized by variable expressivity and incomplete penetrance. Although several chromosomal loci for SHFLD have been identified, the molecular basis and pathogenesis of most SHFLD cases are unknown. In this study we describe three unrelated kindreds, in which SHFLD segregated with distinct but overlapping duplications in 17p13.3, a region previously linked to SHFLD. In a large three-generation family, the disorder was found to segregate with a 254 kb microduplication; a second microduplication of 527 kb was identified in an affected female and her unaffected mother, and a 430 kb microduplication versus microtriplication was identified in three affected members of a multi-generational family. These findings, along with previously published data, suggest that one locus responsible for this form of SHFLD is located within a 173 kb overlapping critical region, and that the copy gains are incompletely penetrant.
authors.affiliation: Department of Pediatrics, Queen's University/Kingston General Hospital, 20 Barrie Street, Kingston, Ontario, Canada. armourc@kgh.kari.net
authors.forename: Christine M
authors.initials: CM
authors.lastname: Armour
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Bulman
authors.forename: Olga
authors.initials: O
authors.lastname: Jarinova
authors.forename: Richard Curtis
authors.initials: RC
authors.lastname: Rogers
authors.forename: Kate B
authors.initials: KB
authors.lastname: Clarkson
authors.forename: Barbara R
authors.initials: BR
authors.lastname: DuPont
authors.forename: Alka
authors.initials: A
authors.lastname: Dwivedi
authors.forename: Frank O
authors.initials: FO
authors.lastname: Bartel
authors.forename: Laura
authors.initials: L
authors.lastname: McDonell
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.forename: David B
authors.initials: DB
authors.lastname: Everman
authors.forename: Gail E
authors.initials: GE
authors.lastname: Graham
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D058674:Chromosome Duplication; D002886:Chromosomes, Human, Pair 17; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013977:Tibia / Q000002:abnormalities; D055815:Young Adult
chemical_list: C082659:ABR protein, human; D020690:GTPase-Activating Proteins