DLX5 ELISA Kit

Objective Split-hand/foot malformation type 1 is an autosomal dominant condition with reduced penetrance and variable expression. We report three individuals from two families with split-hand/split-foot malformation (SHFM) in whom next generation sequencing was performed to investigate the cause of their phenotype. Methods and results The first proband has a de novo balanced translocation t(2;7)(p25.1;q22) identified by karyotyping. Whole genome sequencing showed that the chromosome 7 breakpoint is situated within the SHFM1 locus on chromosome 7q21.3. This separates the DYNC1I1 exons recently identified as limb enhancers in mouse studies from their target genes, DLX5 and DLX6. In the second family, X-linked recessive inheritance was suspected and exome sequencing was performed to search for a mutation in the affected proband and his uncle. No coding mutation was found within the SHFM2 locus at Xq26 or elsewhere in the exome, but a 106 kb deletion within the SHFM1 locus was detected through copy number analysis. Genome sequencing of the deletion breakpoints showed that the DLX5 and DLX6 genes are disomic but the putative DYNC1I1 exon 15 and 17 enhancers are deleted. Conclusions Exome sequencing identified a 106 kb deletion that narrows the SHFM1 critical region from 0.9 to 0.1 Mb and confirms a key role of DYNC1I1 exonic enhancers in normal limb formation in humans.

Specification of neural crest progenitors begins during gastrulation at the neural plate border, long before migration or differentiation. Neural crest cell fate is acquired by progressive activation of discrete groups of transcription factors that appear to be highly conserved in vertebrates; however, comprehensive analysis of their expression has been lacking in chick, an important model system for neural crest development. To address this, we analyzed expression of 10 transcription factors that are known specifiers of neural plate border and neural crest fate and compared them across developmental stages from gastrulation to neural crest migration. Surprisingly, we find that most neural crest specifiers are expressed during gastrulation in chick, concomitant with and in similar domains as neural plate border specifiers. This finding suggests that interactions between these molecules may occur much earlier than previously thought, an important consideration for interpretation of functional studies. Developmental Dynamics 238:716-723, 2009. (C) 2009 Wiley-Liss, Inc.