Rearrangement in the PITX2 and MIPOL1 genes in a patient with a t(4;14) chromosome

Kamnasaran, Deepak; O’Brien, Patricia C.; Zackai, Elaine H.; Muenke, Maximilian; Ferguson‐Smith, Malcolm A.; Cox, Diane W.

doi:10.1038/sj.ejhg.5200963

Cited by 15 publications

(21 citation statements)

References 33 publications

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“…Using in situ hybridization, Peters et al [32] showed that Pax9 is expressed throughout the developing cranial base in mice at E13.5. Biological evidence for other genes in this region also suggests possible roles in facial variation including MIPOL1 , which has been observed to be affected by chromosomal aberrations in patients with craniofacial phenotypes, including holoprosencephaly [35]. Because holoprosencephaly involves alteration in the horizontal spacing of facial structures, variants in genes associated with this condition may also influence measures of craniofacial width in healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

et al. 2016

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Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10−8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

et al. 2016

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“…Chromosome rearrangements involving PITX2 or its surrounding genomic landscape have been observed in 10 ARS patients, 22 -29 and only eight of these cases have been investigated further. 23 -26,28,29 Three of the cases had deletions at the 4q25 breakpoints directly affecting PITX2, 25,28,29 and in five cases the translocation breakpoints were located up to 90 kb upstream of the gene. 23,24,26 In about 14 ARS patients, the genetic defect was a microscopic or submicroscopic deletion of the 4q25 region including PITX2.…”

Section: Pitx2 Defects and Arsmentioning

confidence: 99%

“…23,24,26 In about 14 ARS patients, the genetic defect was a microscopic or submicroscopic deletion of the 4q25 region including PITX2. 24,28,30 -39 In only few cases, the extent of the deletions was characterized by molecular means 25,28,38 and clinical features of these patients do not differ substantially from the phenotypes caused by point mutations of PITX2. 28 Submicroscopic duplications of PITX2 have not been reported in ARS patients, but duplication of the distal region of 4q (including 4q25 and PITX2) has been described in one patient.…”

Section: Pitx2 Defects and Arsmentioning

confidence: 99%

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

2009

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In association withAxenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations Axenfeld -Rieger syndrome (ARS) is a rare autosomal dominant disorder, which encompasses a range of congential malformations affecting the anterior segment of the eye. ARS shows genetic heterogeneity and mutations of the two genes, PITX2 and FOXC1, are known to be associated with the pathogenesis. There are several excellent reviews dealing with the complexity of the phenotype and genotype of ARS. In this study, we will attempt to give a brief review of the clinical features and the relevant diagnostic approaches, together with a detailed review of published PITX2 and FOXC1 mutations.

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“…The PITX2 gene plays a major role in the pathogenesis of ARS, accounting for 40% of classical ARS [Lines et al, 2004;Footz et al, 2009]. In addition to the PITX2 point mutations, several cases of chromosomal aberrations such as interstitial deletions and/or translocations involving the chromosome 4q25 region have been described in patients with clinical features of 7 ARS [Kamnasaran et al, 2003;Trembath et al, 2004;Engenheiro et al, 2007;Tanwar et al, 2009]. Reported balanced translocations disrupt the coding region [Kamnasaran et al, 2003] or the 5 ′ genomic region of the PITX2 gene [Trembath et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of<b><i> PITX2</i></b> and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay

Maldžienė

Preikšaitienė²,

Ignotienė³

et al. 2017

Cytogenet Genome Res

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Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of autosomal dominantly inherited malformations that predominantly affect the eye but are also associated with craniofacial dysmorphism and dental abnormalities. A broad spectrum of genetic alterations involving PITX2 and FOXC1 lead to ARS. We report on a 4-year-old girl with clinical features of ARS and developmental delay due to a de novo apparently balanced pericentric inversion in chromosome 4. This report emphasizes that complementary investigations are necessary to precisely characterize chromosomal rearrangements. Elucidation of the exact genetic cause of ARS is important for comprehensive genetic counseling of the family members and for better patient management.

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Rearrangement in the PITX2 and MIPOL1 genes in a patient with a t(4;14) chromosome

Cited by 15 publications

References 33 publications

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of<b><i> PITX2</i></b> and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay

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