Scientific article

Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region

Published inAmerican journal of medical genetics. Part A, vol. 140, no. 13, p. 1384-1395
Publication date2006

Split-hand/split-foot malformation (SHFM, also called ectrodactyly) is a clinically variable and genetically heterogeneous group of limb malformations. Several SHFM loci have been mapped, including SHFM1 (7q21), SHFM2 (Xq26), SHFM3 (10q24), SHFM4 (3q27) and SHFM5 (2q31). To date, mutations in a gene (TP63) have only been identified for SHFM4. SHFM3 has been shown by pulsed-field gel electrophoresis to be caused by an approximately 500 kb DNA rearrangement at 10q24. This region contains a number of candidate genes for SHFM3, though which gene(s) is (are) involved in the pathogenesis of SHFM3 is not known. Our aim in this study was to improve the diagnosis of SHFM3, and to begin to understand which genes are involved in SHFM3. Here we show, using two different techniques, FISH and quantitative PCR that SHFM3 is caused by a minimal 325 kb duplication containing only two genes (BTRC and POLL). The data presented provide improved methods for diagnosis and begin to elucidate the pathogenic mechanism of SHFM3. Expression analysis of 13 candidate genes within and flanking the duplicated region shows that BTRC (present in three copies) and SUFU (present in two copies) are overexpressed in SHFM3 patients compared to controls. Our data suggest that SHFM3 may be caused by overexpression of BTRC and SUFU, both of which are involved in beta-catenin signalling.

  • Chromosomes, Human, Pair 10/ genetics
  • F-Box Proteins/ genetics
  • Female
  • Foot Deformities, Congenital/epidemiology/ genetics
  • Gene Duplication
  • Hand Deformities, Congenital/epidemiology/ genetics
  • Humans
  • In Situ Hybridization, Fluorescence/ methods
  • India/epidemiology
  • Male
  • Pedigree
  • Polymerase Chain Reaction/ methods
  • Repressor Proteins/genetics
  • Switzerland/epidemiology
  • Beta-Transducin Repeat-Containing Proteins/genetics
Citation (ISO format)
LYLE, Robert et al. Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region. In: American journal of medical genetics. Part A, 2006, vol. 140, n° 13, p. 1384–1395. doi: 10.1002/ajmg.a.31247
Main files (1)
ISSN of the journal1552-4825

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