1. ¹Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
2. ²Solution Oriented Research of Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, Japan
3. ³Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan
4. ⁴National Laboratory of Medical Genetics, Xiangya Hospital, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China
5. ⁵Women and Children's Hospital of Hunan Province, Changsha, China
6. ⁶Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Tokyo, Japan

Correspondence: Lingqian Wu, National Laboratory of Medical Genetics, Xiangya Hospital, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China. E-mail: wulingqian@cnlmg.com

Daisuke Sato and Desheng Liang equally contributed to this study.

Received 26 March 2007; Accepted 2 April 2007; Published online 3 May 2007.

Abstract

Syndactyly occurs as an isolated abnormality or a part of a malformation syndrome. Syndactyly types I, II, III and V have been mapped to chromosomal regions 2q34-q36, 2q31-q32, 6q21-q23.2 and 2q31-q32, respectively, whereas syndactyly type IV (SD4) is extremely rare, and its gene localization has not yet been assigned. The SD4 manifests complete syndactyly of all fingers accompanied with polydactyly, and flexion of the fingers gives the hand a cup-shaped appearance. We performed a linkage and haplotype analysis of a Chinese pedigree with autosomal dominant, non-syndromic SD4 using a set of 406 microsatellite markers. The analysis gave the maximum two-point LOD score of 1.613 at recombination fraction of 0.00 and penetrance of 1.00. Thus, the SD4 locus in the family was likely assigned to a 17.39-cM region at a segment between markers D7S3070 and D7S559 at 7q36, although the LOD score obtained was not high enough to conclude the localization. Analysis of three candidate genes, LMBR1, SHH and ZRS, failed to identify any pathogenic mutations. Our gene mapping may give a clue to identify the putative SD4 gene and provide a better understanding of normal human limb development.