This report describes Robinow syndrome, autosomal dominant 2. The human gene implicated is DVL1, which encodes a cytoplasmic phosphoprotein that regulates cell proliferation by transducing Wnt signaling to down-stream effectors. There is one high-scoring fly ortholog, Dmel\dsh, for which multiple genetic reagents, including amorphic or loss of function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis, have been generated.
Multiple UAS constructs of Hsap\DVL1 have been introduced into flies, including wild-type DVL1 and genes carrying frameshift variants implicated in disease; see the 'Disease-Implicated Variants' table below. Overexpression of both wild-type and mutant Hsap\DVL1 isoforms in the developing wing results in disruptions of planar cell polarity; while expression of mutant isoforms result in additional wing structure phenotypes including thickening of the wing veins, absence of the anterior crossvein, ectopic bristles, and creases. Hsap\DVL1 variants also induce ectopic JNK signalling, and disrupt endogenous canonical WNT signalling.
[updated Mar.2024 by FlyBase; FBrf0222196]
[ROBINOW SYNDROME, AUTOSOMAL DOMINANT 2; DRS2](https://omim.org/entry/616331)
[DISHEVELLED 1; DVL1](https://omim.org/entry/601365)
Robinow syndrome is a skeletal dysplasia characterized by distinctive facial features, including midface hypoplasia, hypertelorism, a short nose, and a broad mouth, known collectively as 'fetal facies.' Additional features include mesomelic dwarfism, macrocephaly, gingival hypertrophy, dental malocclusion, genital hypoplasia, and brachydactyly (summary by Bunn et al., 2015, pmid:25817014). Additionally, increased skull bone density and appendicular osteosclerosis are present in patients with DRS2 (White et al., 2015, pmid:25817016; Bunn et al., 2015, pmid:25817014). [from MIM:616331; 2023.04.28]
Autosomal dominant Robinow syndrome 2 (DRS2) is caused by heterozygous mutation in the DVL1 gene on chromosome 1p36. [from MIM:616331; 2023.04.28]
DVL1, the human homolog of the Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. [provided by RefSeq, Jul 2008]
The DVL1 gene encodes dishevelled-1, a member of a family of intracellular scaffolding proteins that act downstream of transmembrane WNT receptors. [from MIM:601365; 2023.04.28]
Many to one (3 human to 2 Drosophila); DVL1 has one high-scoring Drosophila ortholog, dsh.
High-scoring ortholog of human DVL3, DVL2, and DVL1 (1 Drosophila to 3 human).