title: A single C to T transition in intron 5 of LMBR1 gene is associated with triphalangeal thumb-polysyndactyly syndrome in a Chinese family.
abstract: 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.
authors.affiliation: Institute of Health Science, Shanghai Institutes for Biological Sciences of CAS and Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Tian
authors.forename: Yao-Zhou
authors.initials: YZ
authors.lastname: Shi
authors.forename: Ping-Tong
authors.initials: PT
authors.lastname: Zhou
authors.forename: Zhen-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Run-Zhe
authors.initials: RZ
authors.lastname: Shu
authors.forename: Landian
authors.initials: L
authors.lastname: Hu
authors.forename: Xiangyin
authors.initials: X
authors.lastname: Kong
mesh_terms: D005260:Female; D005385:Fingers / Q000002:abnormalities*; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D013576:Syndactyly / Q000235:genetics*; D013933:Thumb / Q000002:abnormalities*
chemical_list: D053823:Hedgehog Proteins; C485955:LMBR1 protein, human; D008565:Membrane Proteins