Phenotypic and mutational spectrum of ROR2-related Robinow syndrome

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dc.contributor.authorLima A.R.
dc.contributor.authorFerreira B.M.
dc.contributor.authorZhang C.
dc.contributor.authorJolly A.
dc.contributor.authorDu H.
dc.contributor.authorWhite J.J.
dc.contributor.authorDawood M.
dc.contributor.authorLins T.C.
dc.contributor.authorChiabai M.A.
dc.contributor.authorvan Beusekom E.
dc.contributor.authorCordoba M.S.
dc.contributor.authorCaldas Rosa E.C.C.
dc.contributor.authorKayserili H.
dc.contributor.authorKimonis V.
dc.contributor.authorWu E.
dc.contributor.authorMellado C.
dc.contributor.authorAggarwal V.
dc.contributor.authorRichieri-Costa A.
dc.contributor.authorBrunoni D.
dc.contributor.authorCano T.M.
dc.contributor.authorJorge A.A.L.
dc.contributor.authorKim C.A.
dc.contributor.authorHonjo R.
dc.contributor.authorBertola D.R.
dc.contributor.authorDandalo-Girardi R.M.
dc.contributor.authorBayram Y.
dc.contributor.authorGezdirici A.
dc.contributor.authorYilmaz-Gulec E.
dc.contributor.authorGumus E.
dc.contributor.authorYilmaz G.C.
dc.contributor.authorOkamoto N.
dc.contributor.authorOhashi H.
dc.contributor.authorCoban-Akdemir Z.
dc.contributor.authorMitani T.
dc.contributor.authorJhangiani S.N.
dc.contributor.authorMuzny D.M.
dc.contributor.authorRegattieri N.A.P.
dc.contributor.authorPogue R.
dc.contributor.authorPereira R.W.
dc.contributor.authorOtto P.A.
dc.contributor.authorGibbs R.A.
dc.contributor.authorAli B.R.
dc.contributor.authorvan Bokhoven H.
dc.contributor.authorBrunner H.G.
dc.contributor.authorSutton V.R.
dc.contributor.authorLupski J.R.
dc.contributor.authorVianna-Morgante A.M.
dc.contributor.authorCarvalho C.M.B.
dc.contributor.authorMazzeu J.F.
dc.date.accessioned2024-03-12T19:14:39Z
dc.date.available2024-03-12T19:14:39Z
dc.date.issued2022
dc.description.abstract© 2022 Wiley Periodicals LLC.Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.
dc.description.firstpage900
dc.description.issuenumber7
dc.description.lastpage918
dc.description.volume43
dc.identifier.doi10.1002/humu.24375
dc.identifier.issn1098-1004
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/34345
dc.relation.ispartofHuman Mutation
dc.rightsAcesso Restrito
dc.subject.otherlanguagechromosome microarray analysis
dc.subject.otherlanguagecraniofacial morphology
dc.subject.otherlanguageexonic deletion
dc.subject.otherlanguageHPO terms
dc.subject.otherlanguagenext-generation sequencing
dc.subject.otherlanguagequantitative phenotyping cluster heatmap
dc.subject.otherlanguageskeletal dysplasia
dc.subject.otherlanguageWNT pathway
dc.titlePhenotypic and mutational spectrum of ROR2-related Robinow syndrome
dc.typeArtigo
local.scopus.citations10
local.scopus.eid2-s2.0-85129668111
local.scopus.subjectCraniofacial Abnormalities
local.scopus.subjectDwarfism
local.scopus.subjectGenes, Recessive
local.scopus.subjectHumans
local.scopus.subjectLimb Deformities, Congenital
local.scopus.subjectMale
local.scopus.subjectPhenotype
local.scopus.subjectReceptor Tyrosine Kinase-like Orphan Receptors
local.scopus.subjectSyndrome
local.scopus.subjectUrogenital Abnormalities
local.scopus.updated2024-12-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85129668111&origin=inward
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