PRRX1 is mutated in an otocephalic newborn infant conceived by consanguineous parents

Çelik, Tolga; Simsek, PO; Sözen, Tümay; Özyüncü, Özgür; Ge, Utine; Talim, Beril; Yiğit, Serbülent; Boduroğlu, Koray; Kamnasaran, Deepak

doi:10.1111/j.1399-0004.2011.01730.x

Cited by 26 publications

(34 citation statements)

References 15 publications

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“…The finding of PRRX1 de novo frameshift mutations (c.267delA, c.266_269dupAAAA) in 2 unrelated families confirmed its role in autosomal dominant otocephaly [Donnelly et al, 2012;Dasouki et al, 2013]. However, mutations in this gene may be involved in fewer than 15% of ODC cases [Celik et al, 2012]; in the 4 cases reported here, no PRRX1 mutations were identified.…”

Section: Discussionmentioning

confidence: 75%

“…To date, mutations in only 2 genes, OTX2 and PRRX1, have been identified in a small number of ODC cases [Celik et al, 2012;Chassaing et al, 2012]. The most likely explanation for this is that only a small proportion of the causative genes have been identified as yet.…”

Section: Discussionmentioning

confidence: 99%

“…The PRRX1 gene also appeared to be responsible for an autosomal recessive form of otocephaly. An infant born to consanguineous parents carried a nonpolymorphic PRRX1 missense mutation (p.Ala231Pro) inherited from both parents [Celik et al, 2012]. Functional studies indicated that both missense mutations decrease the ability of the mutant protein to regulate the tenascin-C gene promoter, and as a consequence, they were considered deleterious.…”

Section: Discussionmentioning

confidence: 99%

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Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of OTX2

Patat

Ravenswaaij-Arts²,

Tantau³

et al. 2013

Mol Syndromol

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Otocephaly-dysgnathia complex is characterized by mandibular hypo- or aplasia, ear abnormalities, microstomia, and microglossia. Mutations in the orthodenticle homeobox 2 (OTX2) and paired related homeobox 1 (PRRX1) genes have recently been identified in some cases. We screened 4 otocephalic cases for these 2 genes and identified OTX2 mutations in 2 of them, thus confirming OTX2 is implicated in otocephaly. No PRRX1 mutation was identified. Interestingly, ocular involvement is not a constant feature in otocephalic cases with an OTX2 mutation. In one case, the mutation was inherited from a microphthalmic mother. The mechanism underlying this intrafamilial phenotypic variability remains unclear, but other genetic factors are likely to be necessary for the manifestation of the otocephalic phenotype.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of OTX2

Patat

Ravenswaaij-Arts²,

Tantau³

et al. 2013

Mol Syndromol

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“…7,17 Celik et al identified a homozygous lossof-function mutation in the PRRX1 gene in a female infant, born of consanguineous parents, with agnathiaotocephaly complex. 10 The first branchial arch patterning is influenced not only by the complex interplay between the genes and gene products but also by the temporal and spatial relationships between them. The absence of bone morphogenic protein 4 (Bmp4) antagonists, Chordin and Noggin, leads to a spectrum of mandibular hypoplasia.…”

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confidence: 99%

Otocephaly Agnathia-Situs inversus complex with bilateral absence of mandibular nerves

Kandala

Nalluri

2013

Int J Res Med Sci

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“…In humans, several reports have suggested that agnathia-otocephaly complex (AGOTC) could be caused by a heterozygous mutation in the PRRX1 gene (167420) on chromosome 1q24. [21][22][23][24] AGOTC is a rare, often lethal malformation characterized by absence or hypoplasia of the mandible, microstomia, hypoglossia/aglossia, and variable anterior midline fusion of the ears (melotia, synotia) that exhibits many similarities to the hypoplastic features of Prx1 null homozygote mice, 25 which exhibit skeletal defects affecting mandible, limbs, and vertebrae as well as vascular abnormalities and neonatal lethality. In addition, it has been shown that Prx1 colocalized with fibrillins within the developing elastic vascular wall during embryonic development.…”

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confidence: 99%

Role Played by Prx1‐Dependent Extracellular Matrix Properties in Vascular Smooth Muscle Development in Embryonic Lungs

et al. 2015

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Although there are many studies focusing on the molecular pathways underlying lung vascular morphogenesis, the extracellular matrix (ECM)-dependent regulation of mesenchymal cell differentiation in vascular smooth muscle development needs better understanding. In this study, we demonstrate that the paired related homeobox gene transcription factor Prx1 maintains the elastic ECM properties, which are essential for vascular smooth muscle precursor cell differentiation. We have found that Prx1 null mouse lungs exhibit defective vascular smooth muscle development, downregulated elastic ECM expression, and compromised transforming growth factor (TGF)-β localization and signaling. Further characterization of ECM properties using decellularized lung ECM scaffolds derived from Prx1 mice demonstrated that Prx1 is required to maintain lung ECM stiffness. The results of cell culture using stiffness-controlled 2-D and 3-D synthetic substrates confirmed that Prx1-dependent ECM stiffness is essential for promotion of smooth muscle precursor differentiation for effective TGF-β stimulation. Supporting these results, both decellularized Prx1 null lung ECM and Prx1 WT (wild type) ECM scaffolds with blocked TGF-β failed to support mesenchymal cell to 3-D smooth muscle cell differentiation. These results suggest a novel ECMdependent regulatory pathway of lung vascular development wherein Prx1 regulates lung vascular smooth muscle precursor development by coordinating the ECM biophysical and biochemical properties.

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PRRX1 is mutated in an otocephalic newborn infant conceived by consanguineous parents

Cited by 26 publications

References 15 publications

Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of <b><i>OTX2</i></b>

Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of <b><i>OTX2</i></b>

Otocephaly Agnathia-Situs inversus complex with bilateral absence of mandibular nerves

Role Played by Prx1‐Dependent Extracellular Matrix Properties in Vascular Smooth Muscle Development in Embryonic Lungs

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