{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:16:38Z","timestamp":1793049398059,"version":"4.5.0"},"reference-count":86,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T00:00:00Z","timestamp":1530662400000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00c3\u00a7\u00c3\u00a3o de Amparo \u00c3\u00a0 Pesquisa do Estado de S\u00c3\u00a3o Paulo","doi-asserted-by":"publisher","award":["CEPID 2013\/08028-1"],"award-info":[{"award-number":["CEPID 2013\/08028-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2018,1]]},"DOI":"10.1016\/j.ajhg.2017.10.002","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T11:39:27Z","timestamp":1513856367000},"page":"27-43","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":103,"title":["WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome"],"prefix":"10.1016","volume":"102","author":[{"given":"Janson J.","family":"White","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana F.","family":"Mazzeu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Coban-Akdemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavuz","family":"Bayram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Bahrambeigi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hoischen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bregje W.M.","family":"van Bon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alper","family":"Gezdirici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif Yilmaz","family":"Gulec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Ramond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Touraine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Thevenon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Shinawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Beaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Heeley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Hoover-Fong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceren D.","family":"Durmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halil Gurhan","family":"Karabulut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"Marzioglu-Ozdemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atilla","family":"Cayir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet B.","family":"Duz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Seven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Merfort","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Vianna-Morgante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Parrish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Stals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josue","family":"Flores-Daboub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Reid","family":"Sutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.B.","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2017.10.002_bib1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1136\/bmj.1.3516.914","article-title":"The lessons of rare maladies: annual oration before the medical society of London by Sir Archibald Garrod","volume":"1","author":"Garrod","year":"1928","journal-title":"BMJ"},{"key":"10.1016\/j.ajhg.2017.10.002_bib2","first-page":"645","article-title":"A newly recognized dwarfing syndrome","volume":"117","author":"Robinow","year":"1969","journal-title":"Am. J. Dis. Child."},{"key":"10.1016\/j.ajhg.2017.10.002_bib3","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/78113","article-title":"Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome","volume":"25","author":"van Bokhoven","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib4","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/78107","article-title":"Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2","volume":"25","author":"Afzal","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib5","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1046\/j.1365-2443.2003.00662.x","article-title":"The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a\/JNK signalling pathway","volume":"8","author":"Oishi","year":"2003","journal-title":"Genes Cells"},{"key":"10.1016\/j.ajhg.2017.10.002_bib6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/dvdy.22156","article-title":"WNT5A mutations in patients with autosomal dominant Robinow syndrome","volume":"239","author":"Person","year":"2010","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.ajhg.2017.10.002_bib7","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.ajhg.2015.02.015","article-title":"DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome","volume":"96","author":"White","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib8","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajhg.2015.02.010","article-title":"Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome","volume":"96","author":"Bunn","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib9","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.ajhg.2016.01.005","article-title":"DVL3 alleles resulting in a -1 frameshift of the last exon mediate autosomal-dominant Robinow syndrome","volume":"98","author":"White","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib10","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.cell.2014.09.002","article-title":"A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases","volume":"159","author":"Yamamoto","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2017.10.002_bib11","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.cellsig.2009.11.021","article-title":"Dishevelled: The hub of Wnt signaling","volume":"22","author":"Gao","year":"2010","journal-title":"Cell. Signal."},{"key":"10.1016\/j.ajhg.2017.10.002_bib12","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1096\/fj.09-150615","article-title":"Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2","volume":"24","author":"Witte","year":"2010","journal-title":"FASEB J."},{"key":"10.1016\/j.ajhg.2017.10.002_bib13","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0168-9525(02)02770-1","article-title":"Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation?","volume":"18","author":"Mlodzik","year":"2002","journal-title":"Trends Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib14","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.devcel.2011.03.018","article-title":"Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains","volume":"20","author":"Strutt","year":"2011","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ajhg.2017.10.002_bib15","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1056\/NEJMc0910820","article-title":"VANGL2 mutations in human cranial neural-tube defects","volume":"362","author":"Lei","year":"2010","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib16","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/bdra.23002","article-title":"Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis. Birth Defects Res. Part A - Clin","volume":"94","author":"Allache","year":"2012","journal-title":"Mol. Teratol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib17","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1073\/pnas.0712126105","article-title":"Genetic interaction between members of the Vangl family causes neural tube defects in mice","volume":"105","author":"Torban","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2017.10.002_bib18","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/humu.21662","article-title":"Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis","volume":"33","author":"Robinson","year":"2012","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ajhg.2017.10.002_bib19","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/j.1365-2443.2008.01220.x","article-title":"Nucleoredoxin regulates the Wnt\/planar cell polarity pathway in Xenopus","volume":"13","author":"Funato","year":"2008","journal-title":"Genes Cells"},{"key":"10.1016\/j.ajhg.2017.10.002_bib20","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/ncb1405","article-title":"The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-beta-catenin signalling through dishevelled","volume":"8","author":"Funato","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajhg.2015.06.009","article-title":"The genetic basis of Mendelian phenotypes: discoveries, challenges, and opportunities","volume":"97","author":"Chong","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib22","doi-asserted-by":"crossref","first-page":"R68","DOI":"10.1186\/gb-2011-12-7-r68","article-title":"Targeted enrichment beyond the consensus coding DNA sequence exome reveals exons with higher variant densities","volume":"12","author":"Bainbridge","year":"2011","journal-title":"Genome Biol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib23","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/gm543","article-title":"Choice of transcripts and software has a large effect on variant annotation","volume":"6","author":"McCarthy","year":"2014","journal-title":"Genome Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1471-2105-15-30","article-title":"Launching genomics into the cloud: deployment of Mercury, a next generation sequence analysis pipeline","volume":"15","author":"Reid","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.ajhg.2017.10.002_bib25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13073-017-0412-6","article-title":"Lessons learned from additional research analyses of unsolved clinical exome cases","volume":"9","author":"Eldomery","year":"2017","journal-title":"Genome Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib26","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.ajhg.2012.08.005","article-title":"Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth","volume":"91","author":"Fromer","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib27","first-page":"1633","article-title":"Homozygous and hemizygous CNV detection from exome sequencing data in a Mendelian disease cohort","volume":"45","author":"Gambin","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2017.10.002_bib28","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/BF00194629","article-title":"Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA sequence environment","volume":"86","author":"Krawczak","year":"1991","journal-title":"Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib29","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/cge.12401","article-title":"De novo WNT5A-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype","volume":"87","author":"Roifman","year":"2015","journal-title":"Clin. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib30","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1086\/341528","article-title":"Grouping of multiple-lentigines\/LEOPARD and Noonan syndromes on the PTPN11 gene","volume":"71","author":"Digilio","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib31","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ajhg.2010.01.009","article-title":"Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome","volume":"86","author":"Iqbal","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib32","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ajhg.2012.11.011","article-title":"Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia","volume":"92","author":"Below","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1056\/NEJMoa1516767","article-title":"Resolution of disease phenotypes resulting from multilocus genomic variation","volume":"376","author":"Posey","year":"2017","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib34","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/gim.2014.154","article-title":"Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families\u00a0with undiagnosed genetic conditions","volume":"17","author":"Farwell","year":"2015","journal-title":"Genet. Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib35","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1056\/NEJMoa1306555","article-title":"Clinical whole-exome sequencing for the diagnosis of mendelian disorders","volume":"369","author":"Yang","year":"2013","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib36","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1001\/jama.2014.14601","article-title":"Molecular findings among patients referred for clinical whole-exome sequencing","volume":"312","author":"Yang","year":"2014","journal-title":"JAMA"},{"key":"10.1016\/j.ajhg.2017.10.002_bib37","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: a matching tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ajhg.2017.10.002_bib38","doi-asserted-by":"crossref","first-page":"E812","DOI":"10.1073\/pnas.1114802109","article-title":"Wnt\/\u03b2-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled","volume":"109","author":"Tauriello","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2017.10.002_bib39","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1002\/pro.109","article-title":"Sequence requirement and subtype specificity in the high-affinity interaction between human frizzled and dishevelled proteins","volume":"18","author":"Punchihewa","year":"2009","journal-title":"Protein Sci."},{"key":"10.1016\/j.ajhg.2017.10.002_bib40","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1093\/hmg\/ddv088","article-title":"A mutation in FRIZZLED2 impairs Wnt signaling and causes autosomal dominant omodysplasia","volume":"24","author":"Saal","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib41","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1353\/pbm.1969.0039","article-title":"On lumpers and splitters, or the nosology of genetic disease","volume":"12","author":"McKusick","year":"1969","journal-title":"Perspect. Biol. Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib42","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1101\/gr.156075.113","article-title":"Deletions of recessive disease genes: CNV contribution to carrier states and disease-causing alleles","volume":"23","author":"Boone","year":"2013","journal-title":"Genome Res."},{"key":"10.1016\/j.ajhg.2017.10.002_bib43","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ajhg.2015.12.008","article-title":"Recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic TANGO2 mutations","volume":"98","author":"Lalani","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib44","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ajhg.2016.08.007","article-title":"Recurrent de novo and biallelic variation of ATAD3A, encoding a mitochondrial membrane protein, results in distinct neurological syndromes","volume":"99","author":"Harel","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib45","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1093\/hmg\/ddv146","article-title":"Alu-mediated diverse and complex pathogenic copy-number variants within human chromosome 17 at p13.3","volume":"24","author":"Gu","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib46","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1126\/science.aaa8391","article-title":"DNA REPAIR. Mus81 and converging forks limit the mutagenicity of replication fork breakage","volume":"349","author":"Mayle","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2017.10.002_bib47","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nrg.2015.25","article-title":"Mechanisms underlying structural variant formation in genomic disorders","volume":"17","author":"Carvalho","year":"2016","journal-title":"Nat.\u00a0Rev. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib48","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1006\/geno.1996.4493","article-title":"Cloning and characterization of the nucleoredoxin gene that encodes a novel nuclear protein related to thioredoxin","volume":"39","author":"Kurooka","year":"1997","journal-title":"Genomics"},{"key":"10.1016\/j.ajhg.2017.10.002_bib49","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.cub.2010.09.065","article-title":"Nucleoredoxin sustains Wnt\/\u03b2-catenin signaling by retaining a pool of inactive dishevelled protein","volume":"20","author":"Funato","year":"2010","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib50","doi-asserted-by":"crossref","first-page":"e1000759","DOI":"10.1371\/journal.pgen.1000759","article-title":"Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin","volume":"5","author":"Boles","year":"2009","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib51","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/ajmg.a.31592","article-title":"Clinical characterization of autosomal dominant and recessive variants of Robinow syndrome","volume":"143","author":"Mazzeu","year":"2007","journal-title":"Am. J. Med. Genet. A."},{"key":"10.1016\/j.ajhg.2017.10.002_bib52","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1101\/gad.1022203","article-title":"Coactivation of Rac and Rho by Wnt\/Frizzled signaling is required for vertebrate gastrulation","volume":"17","author":"Habas","year":"2003","journal-title":"Genes Dev."},{"key":"10.1016\/j.ajhg.2017.10.002_bib53","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1038\/nature05817","article-title":"Heparan sulphate proteoglycans fine-tune mammalian physiology","volume":"446","author":"Bishop","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2017.10.002_bib54","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.ajhg.2009.05.002","article-title":"Mutations in the heparan-sulfate proteoglycan glypican 6 impair endochondral ossification and cause recessive omodysplasia","volume":"84","author":"Campos-Xavier","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib55","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/ng0396-241","article-title":"Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome","volume":"12","author":"Pilia","year":"1996","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib56","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1242\/dev.00435","article-title":"Role of glypican 4 in the regulation of convergent extension movements during gastrulation in Xenopus laevis","volume":"130","author":"Ohkawara","year":"2003","journal-title":"Development"},{"key":"10.1016\/j.ajhg.2017.10.002_bib57","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/22336","article-title":"The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila","volume":"400","author":"Tsuda","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2017.10.002_bib58","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1002\/ajmg.a.33450","article-title":"Novel duplication in glypican-4 as an apparent cause of Simpson-Golabi-Behmel syndrome","volume":"152A","author":"Waterson","year":"2010","journal-title":"Am. J. Med. Genet. A."},{"key":"10.1016\/j.ajhg.2017.10.002_bib59","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/path.2824","article-title":"Cartilage ultrastructure in proteoglycan-deficient zebrafish mutants brings to light new candidate genes for human skeletal disorders","volume":"223","author":"Wiweger","year":"2011","journal-title":"J.\u00a0Pathol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib60","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1001\/archinte.1939.00180230108008","article-title":"Relation of hereditary pattern to clinical severity as illustrated by peroneal atrophy","volume":"63","author":"Allan","year":"1939","journal-title":"Arch. Intern. Med. (Chic.)"},{"key":"10.1016\/j.ajhg.2017.10.002_bib61","first-page":"80","article-title":"The detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type","volume":"8","author":"Morton","year":"1956","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib62","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/mgg3.233","article-title":"Lessons learned from the search for genes responsible for rare Mendelian disorders","volume":"4","author":"Sobreira","year":"2016","journal-title":"Mol. Genet. Genomic Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib63","doi-asserted-by":"crossref","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: Online Mendelian Inheritance in Man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ajhg.2017.10.002_bib64","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nrg1383","article-title":"From syndrome families to functional genomics","volume":"5","author":"Brunner","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib65","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ydbio.2007.03.011","article-title":"Wnt5a functions in planar cell polarity regulation in mice","volume":"306","author":"Qian","year":"2007","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib66","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1242\/dev.126.6.1211","article-title":"A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo","volume":"126","author":"Yamaguchi","year":"1999","journal-title":"Development"},{"key":"10.1016\/j.ajhg.2017.10.002_bib67","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1242\/dev.023820","article-title":"Noncanonical frizzled signaling regulates cell polarity of growth plate chondrocytes","volume":"136","author":"Li","year":"2009","journal-title":"Development"},{"key":"10.1016\/j.ajhg.2017.10.002_bib68","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/dvdy.10466","article-title":"Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome","volume":"229","author":"Schwabe","year":"2004","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.ajhg.2017.10.002_bib69","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ydbio.2013.10.013","article-title":"Regulation of cell polarity in the cartilage growth plate and perichondrium of metacarpal elements by HOXD13 and WNT5A","volume":"385","author":"Kuss","year":"2014","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib70","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/329549a0","article-title":"Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila","volume":"329","author":"Vinson","year":"1987","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2017.10.002_bib71","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1101\/gad.8.1.118","article-title":"The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal","volume":"8","author":"Klingensmith","year":"1994","journal-title":"Genes Dev."},{"key":"10.1016\/j.ajhg.2017.10.002_bib72","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1371\/journal.pbio.0040115","article-title":"Purified Wnt5a protein activates or inhibits \u03b2-catenin-TCF signaling depending on receptor context","volume":"4","author":"Mikels","year":"2006","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ajhg.2017.10.002_bib73","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/382225a0","article-title":"A new member of the frizzled family from Drosophila functions as a Wingless receptor","volume":"382","author":"Bhanot","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2017.10.002_bib74","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/emboj.2009.322","article-title":"Wnt5a regulates distinct signalling pathways by binding to Frizzled2","volume":"29","author":"Sato","year":"2010","journal-title":"EMBO J."},{"key":"10.1016\/j.ajhg.2017.10.002_bib75","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.270.5234.296","article-title":"Requirement for generation of H2O2 for platelet-derived growth factor signal transduction","volume":"270","author":"Sundaresan","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2017.10.002_bib76","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1242\/dev.127.14.3141","article-title":"Dual roles of Wnt signaling during chondrogenesis in the chicken limb","volume":"127","author":"Hartmann","year":"2000","journal-title":"Development"},{"key":"10.1016\/j.ajhg.2017.10.002_bib77","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/sj.cr.7290232","article-title":"Characterization of function of three domains in dishevelled-1: DEP domain is responsible for membrane translocation of dishevelled-1","volume":"14","author":"Pan","year":"2004","journal-title":"Cell Res."},{"key":"10.1016\/j.ajhg.2017.10.002_bib78","doi-asserted-by":"crossref","first-page":"23520","DOI":"10.1074\/jbc.M114.590638","article-title":"Functional analysis of dishevelled-3 phosphorylation identifies distinct mechanisms driven by casein kinase 1\u03f5 and frizzled5","volume":"289","author":"Bernat\u00edk","year":"2014","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ajhg.2017.10.002_bib79","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1073\/pnas.1200421109","article-title":"Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis","volume":"109","author":"Ho","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2017.10.002_bib80","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1084\/jem.20062525","article-title":"Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification","volume":"204","author":"Morita","year":"2007","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib81","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1086\/514346","article-title":"Mendelian Inheritance in Man and its online version, OMIM","volume":"80","author":"McKusick","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib82","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ajhg.2014.06.014","article-title":"The Alu-rich genomic architecture of SPAST predisposes to diverse and functionally distinct disease-associated CNV alleles","volume":"95","author":"Boone","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2017.10.002_bib83","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1097\/GIM.0b013e3182106775","article-title":"Alu-specific microhomology-mediated deletion of the final exon of SPAST in three unrelated subjects with hereditary spastic paraplegia","volume":"13","author":"Boone","year":"2011","journal-title":"Genet. Med."},{"key":"10.1016\/j.ajhg.2017.10.002_bib84","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/352544a0","article-title":"Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli","volume":"352","author":"Trinh","year":"1991","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2017.10.002_bib85","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.celrep.2015.07.023","article-title":"Exome sequence analysis suggests that genetic burden contributes to phenotypic variability and complex neuropathy","volume":"12","author":"Gonzaga-Jauregui","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.ajhg.2017.10.002_bib86","doi-asserted-by":"crossref","first-page":"4468","DOI":"10.1074\/jbc.271.8.4468","article-title":"A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled","volume":"271","author":"Wang","year":"1996","journal-title":"J.\u00a0Biol. Chem."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929717304226?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929717304226?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:17:46Z","timestamp":1762078666000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929717304226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":86,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["S0002929717304226"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2017.10.002","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2017.10.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 American Society of Human Genetics.","name":"copyright","label":"Copyright"}]}}