A single C to T transition in intron 5 of LMBR1 gene is associated with triphalangeal thumb-polysyndactyly syndrome in a Chinese family

Biochem Biophys Res Commun. 2007 Apr 6;355(2):312-7. doi: 10.1016/j.bbrc.2007.01.129. Epub 2007 Feb 2.


Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a type of human hand-foot malformation. In this study, we collected data from a Chinese family with TPT-PS and mapped the disease region to chromosome 7q36. By using a fine mapping study and a haplotype analysis, we narrowed the affected region to 1.7cM between markers D7S2465 and D7S2423, which contains four candidate genes: HLXB9, LMBR1, NOM1, and RNF32. By sequence analysis, we found no sequence alterations, which are specific to the patients in the transcribed regions and in the intron-exon boundaries among the four genes. After closely examining intron 5 of the LMBR1 gene, we discovered a single C to T transition in the affected TPT-PS individuals of the Chinese subject family. The position of this C to T transition is located close to other sequence alterations involved in several preaxial polydactyly (PPD) families, supporting the notion that intron 5 of LMBR1 contains a cis-acting regulator of limb-specific Sonic Hedgehog (SHH). We postulate that the disruption of this cis-regulator via a single C to T transition results in the dysregulation of SHH, which leads to the TPT-PS found in this case.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Fingers / abnormalities*
  • Hedgehog Proteins / genetics
  • Humans
  • Introns*
  • Male
  • Membrane Proteins / genetics*
  • Pedigree
  • Syndactyly / genetics*
  • Thumb / abnormalities*


  • Hedgehog Proteins
  • LMBR1 protein, human
  • Membrane Proteins