HGNC Approved Gene Symbol: DVL3
Cytogenetic location: 3q27.1 Genomic coordinates (GRCh38): 3:184,155,377-184,173,614 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3q27.1 | Robinow syndrome, autosomal dominant 3 | 616894 | Autosomal dominant | 3 |
The Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein (Klingensmith et al., 1994) that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. Pizzuti et al. (1996) noted that dsh is required for the function of the wingless gene product wg, a segment polarity gene homologous to the mammalian protooncogene WNT1 (164820). Pizzuti et al. (1996) reported the isolation and chromosomal mapping of 2 human dsh homologs, designated DVL1 (601365) and DVL3 by them. The human dsh homologs were isolated from a fetal brain cDNA library. DVL3 encodes a predicted 716-amino acid polypeptide that shows 74% nucleotide homology with human DVL1 and 71% homology with the mouse Dvl1 gene. DVL1 and DVL3 share 64% amino acid identity, with greater homology in the N-terminal region. Hybridization of poly(A) mRNA with the DVL3 cDNA revealed a 2.9-kb transcript with abundant expression in skeletal muscle, pancreas and heart. Transcripts of 5.9 kb and 5.0 kb were also detected in skeletal muscle, adult liver, adult heart, pancreas, and placenta. The 5.9-kb form was abundant in fetal tissues, whereas the 5.0-kb form was absent in these tissues.
Bui et al. (1997) also isolated human DVL3, which shares 98% amino acid identity with mouse Dvl3 and 49% with Drosophila dsh. Bui et al. (1997) detected expression of DVL3 mRNA in B cells, breast, kidney, bladder, endometrium, and 2 primary endometrial cultures. It was detected equally in normal human breast tissues and tumors and in colorectal samples of normal tissues, polyps, and tumors.
Semenov and Snyder (1997) isolated 3 human genes encoding proteins homologous to Drosophila dsh. The cDNA sequence of DVL3 reported by Semenov and Snyder (1997) differs from the previously reported sequences deposited in GenBank.
By PCR with DNA from rodent-human somatic cell hybrids and DVL3 specific primers, Pizzuti et al. (1996) mapped the DVL3 gene to chromosome 3. They regionally assigned the gene to 3q27 by fluorescence in situ hybridization.
Bui et al. (1997) confirmed the chromosomal localization of DVL3 to 3q27.
In 5 patients with Robinow syndrome-3 (DRS3; 616894), White et al. (2016) identified heterozygosity for mutations in the DVL3 gene (601368.0001-601368.0005), all predicted to result in a frameshift to the -1 reading frame and a premature termination codon in the last exon. The mutations arose de novo or were inherited from an affected parent, and none were found in an in-house database of more than 4,200 exomes or in public variant databases.
In a 38-year-old woman (patient 015902) with Robinow syndrome-3 (DRS3; 616894), White et al. (2016) identified heterozygosity for a 1-bp deletion (c.1749delC, NM_004423.3) in exon 15 of the DVL3 gene, predicted to result in a frameshift to the -1 reading frame and a premature termination codon in the last exon (Ser583ArgfsTer85). Her affected mother was also heterozygous for the deletion, which was not found in an in-house database of more than 4,200 exomes, the Atherosis Risk in Communities database of approximately 4,000 individuals, or the 1000 Genomes Project, NHLBI Exome Sequencing Project, dbSNP, or ExAC databases.
In a 35-year-old woman (patient BAB4569) with Robinow syndrome-3 (DRS3; 616894), White et al. (2016) identified heterozygosity for a de novo 1-bp deletion (c.1716delC, NM_004423.3) in exon 15 of the DVL3 gene, predicted to result in a frameshift to the -1 reading frame and a premature termination codon in the last exon (Ser573ValfsTer95). The deletion was not found in an in-house database of more than 4,200 exomes, the Atherosis Risk in Communities database of approximately 4,000 individuals, or the 1000 Genomes Project, NHLBI Exome Sequencing Project, dbSNP, or ExAC databases.
In a 14-year-old girl (patient BAB7990) with Robinow syndrome-3 (DRS3; 616894), White et al. (2016) identified heterozygosity for a 1-bp deletion (c.1585delG, NM_004423.3) in exon 14 of the DVL3 gene, predicted to result in a frameshift to the -1 reading frame and a premature termination codon in the last exon (Ala529ProfsTer139). Her affected father was also heterozygous for the deletion, which was not found in an in-house database of more than 4,200 exomes, the Atherosis Risk in Communities database of approximately 4,000 individuals, or the 1000 Genomes Project, NHLBI Exome Sequencing Project, dbSNP, or ExAC databases.
In a 12-year-old boy (patient BAB7982) with Robinow syndrome-3 (DRS3; 616894), White et al. (2016) identified heterozygosity for a de novo splice site mutation (c.1715-1G-A, NM_004423.3) in intron 14 of the DVL3 gene, predicted to result in a frameshift to the -1 reading frame and a premature termination codon in the last exon. The mutation was not found in an in-house database of more than 4,200 exomes, the Atherosis Risk in Communities database of approximately 4,000 individuals, or the 1000 Genomes Project, NHLBI Exome Sequencing Project, dbSNP, or ExAC databases.
In an individual (patient BAB7985) with Robinow syndrome-3 (DRS3; 616894), White et al. (2016) identified heterozygosity for a splice site mutation (c.1715-2A-G, NM_004423.3) in intron 14 of the DVL3 gene, predicted to result in a frameshift to the -1 reading frame and a premature termination codon in the last exon. The mutation was not found in an in-house database of more than 4,200 exomes, the Atherosis Risk in Communities database of approximately 4,000 individuals, or the 1000 Genomes Project, NHLBI Exome Sequencing Project, dbSNP, or ExAC databases.
Bui, T. D., Beier, D. R., Jonssen, M., Smith, K., Dorrington, S. M., Kaklamanis, L., Kearney, L., Regan, R., Sussman, D. J., Harris, A. L. cDNA cloning of a human dishevelled DVL-3 gene, mapping to 3q27, and expression in human breast and colon carcinomas. Biochem. Biophys. Res. Commun. 239: 510-516, 1997. [PubMed: 9344861] [Full Text: https://doi.org/10.1006/bbrc.1997.7500]
Klingensmith, J., Nusse, R., Perrimon, N. The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to wingless signal. Genes Dev. 8: 118-130, 1994. [PubMed: 8288125] [Full Text: https://doi.org/10.1101/gad.8.1.118]
Pizzuti, A., Amati, F., Calabrese, G., Mari, A., Colosimo, A, Silani, V., Giardino, L., Ratti, A., Penso, D., Calza, L., Palka, G., Scarlato, G., Novelli, G., Dallapicolla, B. cDNA characterization and chromosomal mapping of two human homologs of the Drosophila dishevelled polarity gene. Hum. Molec. Genet. 5: 953-958, 1996. [PubMed: 8817329] [Full Text: https://doi.org/10.1093/hmg/5.7.953]
Semenov, M. V., Snyder, M. Human dishevelled genes constitute a DHR-containing multigene family. Genomics 42: 302-310, 1997. [PubMed: 9192851] [Full Text: https://doi.org/10.1006/geno.1997.4713]
White, J. J., Mazzeu, J. F., Hoischen, A., Bayram, Y., Withers, M., Gezdirici, A., Kimonis, V., Steehouwer, M., Jhangiani, S. N., Muzny, D. M., Gibbs, R. A., Baylor-Hopkins Center for Mendelian Genetics, van Bon, B. W. M., Sutton, V. R., Lupski, J. R., Brunner, H. G., Carvalho, C. M. B. DVL3 alleles resulting in a -1 frameshift of the last exon mediate autosomal-dominant Robinow syndrome. Am. J. Hum. Genet. 98: 553-561, 2016. [PubMed: 26924530] [Full Text: https://doi.org/10.1016/j.ajhg.2016.01.005]