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Genetic heterogeneity in type III familial cutaneous syndactyly and linkage to chromosome 7q36

Authors


  • Additional supporting information may be found in the online version of this article.
  • Mohammad M. Al-Qattan and Hanan E. Shamseldin contributed equally to this work.
  • Conflict of interest: none.

Correspondence to:

Fowzan S Alkuraya, M.D., Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO Box 3354, Riyadh 11211, Saudi Arabia.

Email: falkuraya@kfshrc.edu.sa

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. © 2013 Wiley Periodicals, Inc.

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