Genomic rearrangement at 10q24 in non-syndromic split-hand/split-foot malformation
Split-hand/split-foot malformation (SHFM) is a congenital limb malformation characterized by a median cleft of hand and/or foot due to the absence of central rays. Five loci for syndromic and non-syndromic SHFM, termed SHFM1-5, have been mapped to date. Recently, a 0.5 Mb tandem genomic duplication was found at chromosome 10q24 in SHFM3 families. To refine the minimum duplicated region and to further characterize the SHFM3 locus, we screened 28 non-syndromic SHFM families for tandem genomic duplication of 10q24 by Southern blot and sequence analysis of the dactylin gene. Of 28 families, only two showed genomic rearrangements. Representative patients from the two families exhibit typical SHFM, with symmetrically affected hands and feet. One patient is a familial case with a 511,661 bp tandem duplication, whereas the second is a sporadic case arising from a de novo, 447,338 bp duplication of maternal origin. The smaller duplication in the second patient contained the LBX1, BTRC, POLL, and DPCD genes and a disrupted extra copy of the dactylin gene, and was nearly identical to the smallest known duplicated region of SHFM3. Our results indicate that genomic rearrangement of SHFM3 is rare among non-syndromic SHFM patients and emphasize the importance of screening for genomic rearrangements even in sporadic cases of SHFM.
KeywordsGenomic Rearrangement Duplicate Region Cosmid Clone Extra Band Flank Intronic Sequence
We thank the patients and their families who participated in this study, and we thank Drs. Kozo Shimada, Koichi Tada, Hidehiko Kawabata, Toshihiko Ogino, Daisuke Ishigaki, Tadao Kojima, Nobuhiko Haga, Eiji Nii, Masaaki Shima, and Shigeo Kure for kindly providing patient samples and clinical information. This work was supported by the twentyfrirst Century COE program from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
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