title: Somatic/gonadal mosaicism in a syndromic form of ectrodactyly, including eye abnormalities, documented through array-based comparative genomic hybridization.
abstract: 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 (SHFM1 at 7q21-q22), SHFM2 (Xq26), SHFM3 (FBXW4/DACTYLIN at 10q24), SHFM4 (TP63 at 3q27), and SHFM5 (DLX1 and DLX 2 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 ectrodacytyly, 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.
authors.affiliation: Group for Advanced Molecular Investigation, Graduate Program in Health Sciences, Center for Biological and Health Sciences, Pontifícia Universidade Católica do Parana, Curitiba, PR, Brazil.
authors.forename: Aguinaldo Bonalumi
authors.initials: AB
authors.lastname: Filho
authors.forename: Josiane
authors.initials: J
authors.lastname: Souza
authors.forename: Fábio Rueda
authors.initials: FR
authors.lastname: Faucz
authors.forename: Vanessa Santos
authors.initials: VS
authors.lastname: Sotomaior
authors.forename: Barbara
authors.initials: B
authors.lastname: Dupont
authors.forename: Frank
authors.initials: F
authors.lastname: Bartel
authors.forename: Reycel
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Cindy
authors.initials: C
authors.lastname: Skinner
authors.forename: Sarah
authors.initials: S
authors.lastname: Alliman
authors.forename: Salmo
authors.initials: S
authors.lastname: Raskin
mesh_terms: D000328:Adult; D005124:Eye Abnormalities / Q000235:genetics*; D005385:Fingers / Q000002:abnormalities; D006228:Hand Deformities, Congenital / Q000235:genetics; D006801:Humans; D017880:Limb Deformities, Congenital; D008297:Male; D009030:Mosaicism; D009693:Nucleic Acid Hybridization