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On the basis of the Human Cytogenetic Database, a computerized catalog of the clinical phenotypes associated with cytogenetically detectable human chromosome aberrations, we collected from the literature 102 cases with chromosomal aberrations and split hand/foot malformation or absent fingers/toes. Statistical analysis revealed a highly significant association (P&lt;0.001) between the malformation and the chromosomal bands 4q32-q35, 5q15, 6q16-q22 and 7q11.2-q22 (SHFM1). Considering these findings, we suggest additional SHFM loci on chromosome 4q, 6q and probably 5q. The regions 4q and 6q have already been discussed in the literature as additional SHFM loci. We now show further evidence. In the proposed regions, there are interesting candidate genes such as, on 4q: HAND2, FGF2, LEF1 and BMPR1B; on 5q: MSX2, FLT4, PTX1 and PDLIM7; and on 6q: SNX3, GJA1, HEY2 and Tbx18.

4q32–q35 and 6q16–q22 are valuable candidate regions for split hand/foot malformation