title: Genetic heterogeneity in type III familial cutaneous syndactyly and linkage to chromosome 7q36.
abstract: The ZRS (zone of polarizing activity regulatory sequence) is a long-range limb-specific Sonic Hedgehog (SHH) enhancer. In humans, the ZRS is located in chromosome 7q36 within intron 5 of LMBR1; approximately 1 Mb telomeric of SHH. Point mutations and duplications of the ZRS lead to a variable phenotype of preaxial polydactyly/triphalangeal thumb, tibial hypoplasia, radial ray deficiency, and type IV familial syndactyly (syndactyly of all digits with polydactyly). The ZRS is conserved among mammals and fish and regulates the expression of SHH. In mice, the conserved ZRS within the Lmbr1 gene is found in chromosome 5. The Hammertoe (Hm) mouse mutants have a mutation in the Lmbr1 locus and show syndactyly of digits 2-5 without polydactyly. No previous reports have described isolated syndactyly without polydactyly to be related to the LMBR1 locus in humans. In this report, we describe a family with simple cutaneous syndactyly involving digits 2-5, without polydactyly which is consistent with the phenotype of type III syndactyly. The locus we identified on ch7q36.3 is syntenic to the Hm locus; and affected members of the family had a phenotype analogous to Hm. Hence, the type of syndactyly described in the current report may be equivalent to Hm mice.
authors.affiliation: Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Al-Qattan
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al Mazyad
authors.forename: Saud
authors.initials: S
authors.lastname: Al Deghaither
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000818:Animals; D002897:Chromosomes, Human, Pair 7; D018031:Connexin 43 / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005190:Family; D005385:Fingers / Q000002:abnormalities*; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D013576:Syndactyly / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; C485955:LMBR1 protein, human; C417920:Lmbr1 protein, mouse; D008565:Membrane Proteins; D014157:Transcription Factors