Somatic/Gonadal Mosaicism in a Syndromic Form of Ectrodactyly, Including Eye Abnormalities, Documented Through Array-Based Comparative Genomic Hybridization

摘要

Split hand/foot malformation (SHFM) is characterized by underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. SHFM is a heterogeneous condition caused by abnormalities at one of multiple loci, including SHFM1 (SBFM1 at 7q21-q22), SHFM2 (Xq26), SHFM3 (FBXW4/DACTYLIN at 10q24), SHFM4 (TP63 at 3q27), and SHFM5 (DLX1 and DLX2 at 2q31). SHFM3 is unique in that it is caused by submicroscopic tandem chromosome duplications of FBXW4/DACTYLIN. In order to show that array -based comparative genomic hybridization should be considered an essential aspect of the genetic analysis of patients with SHFM, we report on a family with two brothers who have ectrodactyly. Interestingly, both also have ocular abnormalities. Their sister and both parents are healthy. DNA of all five family members was analyzed using oligonucleotide-based DNA microarray and quantitative PCR. The two affected brothers were found to have a small duplication of approximately 539 kb at 10q24.32. The patients' sister and father do not have the microduplication, but qPCR showed that mother's DNA carries the duplication in 20% of blood lymphocytes. In this family, two children were affected with ectrodactyly having a duplication over the SHFM3 locus. The mother, who shows no clinical features of ectroda-cytyly, is a mosaic for the same duplication. Therefore,' we demonstrate that somatic/gonadal mosaicism is a mechanism that gives rise to SHFM. We also suggest that ocular abnormalities may be part of the clinical description of SHFM3.