Abstract
Split hand/foot malformation (SHFM) is a limb malformation with underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. There are six types of SHFM. Here, we report a boy with SHFM type 3 having normal 4th and 5th digits, absent 2nd and 3rd digits, and a 4th finger flexion deformity, as well as absent 2nd, 3rd and 4th toes bilaterally. His father, two paternal uncles, and two paternal first cousins have similar phenotype. Chromosome analysis showed a normal male karyotype. A 514 kb gain at 10q24.31–q24.32 (chr10:102,962,134–103,476,346, hg19) was identified using 6.0 Single nucleotide polymorphism (SNP) microarray, resulting in the duplication of nine genes, including BTRC and FBXW4. A detailed systematic review of literature and mapping of breakpoints using microarray data from all reported cases in PubMed and DECIPHER were conducted, and exon 1 of BTRC gene was identified as the critical region responsible for the SHFM3 phenotype. The potential mechanism and future studies of this critical region causing the SHFM3 phenotype are discussed.
Highlights
Split-hand/foot malformation (SHFM) is a limb malformation with underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits
The shortest duplication resulting in classical SHFM phenotype is 394 kb at 10q24.31–q24.32 containing LBX1, FLJ41350, AX747408, BTRC, POLL, and a portion of DPCD from centromeric to telomeric direction in Patient 17
Duplication of sequence in the exon 1 of BTRC is responsible for the formation of SHFM3 phenotype, which may be via cis-acting or trans-acting effects on genes or regulatory sequences involved in the limb development pathway
Summary
Split-hand/foot malformation (SHFM) is a limb malformation with underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. It is a rare condition, affecting 1 in 8500–25,000 newborns. We report a boy with SHFM type 3, having 514 kb duplication at 10q24.31–q24.32 identified using 6.0 SNP microarray. A literature review of reported cases, mapping of breakpoints using microarray data to identify the critical region responsible for the SHFM3 phenotype, and discussion of the potential mechanism and future studies of this critical region causing the SHFM3 phenotype are presented below
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