* 173490
PLATELET-DERIVED GROWTH FACTOR RECEPTOR, ALPHA; PDGFRA
Alternative titles; symbols
PDGFR2
Other entities represented in this entry:
HGNC Approved Gene Symbol: PDGFRA
Cytogenetic location: 4q12 Genomic coordinates (GRCh38): 4:54,229,088-54,298,246 (from NCBI)
Gene-Phenotype Relationships
| Location | Phenotype | Phenotype MIM number |
Inheritance | Phenotype mapping key |
|---|---|---|---|---|
| 4q12 | Gastrointestinal stromal tumor, somatic | 606764 | 3 | |
| Hypereosinophilic syndrome, idiopathic, resistant to imatinib | 607685 | Somatic mutation; Isolated cases | 3 |
TEXT
Cloning and Expression
Matsui et al. (1989) identified a genomic sequence and a cloned cDNA for a novel receptor-like gene of the PDGF receptor/CSF1 receptor family. The gene recognized a 6.4-kb transcript that was coexpressed in normal human tissues with the 5.3-kb PDGF receptor mRNA. The characteristics of the new receptor were different from the previously known one (PDGFR1; 173410). Matsui et al. (1989) suggested that the existence of genes encoding 2 PDGF receptors that interact in a distinct manner with 3 different PDGF isoforms may confer regulatory flexibility in functional responses to PDGF.
PDGFRA Fusion Genes
Chronic myeloid leukemia (CML; 608232) is characterized by the presence of the BCR (151410)/ABL (189980) fusion gene, usually in association with a t(9;22)(q34;q11) chromosomal translocation. Baxter et al. (2002) reported the identification and cloning of a rare variant translocation, t(4;22)(q12;q11), in 2 patients with a CML-like myeloproliferative disease. An unusual in-frame BCR/PDGFRA fusion mRNA was identified in both patients, with either BCR exon 7 or exon 12 fused to short BCR intron-derived sequences, which were in turn fused to part of PDGFRA exon 12. Sequencing of the genomic breakpoint junctions showed that the chromosome 22 breakpoints fell in BCR introns, whereas the chromosome 4 breakpoints were within PDGFRA exon 12.
Cools et al. (2003) demonstrated that idiopathic hypereosinophilic syndrome (607685) is often caused by an interstitial deletion on chromosome 4q12 resulting in fusion of PDGFRA and FIP1L1 (607686), a neighboring gene. The PDGFRA-FIP1L1 gene is a constitutively activated tyrosine kinase that transforms hematopoietic cells and is a therapeutic target of imatinib. Cools et al. (2003) identified the PDGFRA-FIP1L1 gene in 9 of 16 patients with idiopathic hypereosinophilic syndrome and in 5 of 9 patients with responses to imatinib that lasted more than 3 months. Relapse in one patient correlated with the appearance of a thr674-to-ile mutation in the PDGFRA gene (T674I; 173490.0008) that conferred resistance to imatinib.
Gene Structure
Kawagishi et al. (1995) isolated genomic clones encoding PDGFRA and showed that the gene contains 23 exons spanning about 65 kb. The first noncoding exon is followed by a large intron of approximately 23 kb.
Gene Function
In animal studies, Helwig et al. (1995) found evidence for a functional relation between PDGFR-alpha and PAX1 (167411). Using the human PDGFRA promoter linked to a luciferase reporter, Joosten et al. (1998) showed that PAX1 acts as a transcriptional activator of the PDGFRA gene in differentiated human embryonal carcinoma cells. Two Pax1 variants, a murine Pax1 mutation and a PAX1 sequence variant identified by Hol et al. (1996) in a patient with spina bifida (see 182940), showed either no or less transcriptional activity towards PFGFRA.
Using transfected porcine aortic endothelial cells, Lindholm et al. (2000) found that the SH2 domain of human SHF (617313) bound to phosphorylated tyr720 in PDGF-alpha receptor, but not to phosphorylated PDGF-beta receptor (PDGFRB; 173410). NIH3T3 mouse fibroblasts overexpressing SHF had significantly lower rates of apoptosis in response to PDGF-alpha (PDGFA; 173430). Lindholm et al. (2000) concluded that SHF plays a role in PDGF receptor signaling and regulation of apoptosis.
Phillips et al. (2001) determined that the phox homology domain of sorting nexin-15 (SNX15; 605964) associates with platelet-derived growth factor receptors. Immunoprecipitation experiments demonstrated that excess SNX15 decreases the internalization and degradation of PDGFR.
Considerable insight into the role of the Sonic hedgehog (600725) pathway in vertebrate development and human cancers came from the discovery that mutations in 'Patched' (PTCH; 601309) are associated with basal cell nevus syndrome (BCNS; 109400), an autosomal dominant disorder combining developmental anomalies and tumors, particularly basal cell carcinomas (BCCs). Sporadic BCCs, the most common human cancer, consistently have abnormalities in the hedgehog pathway, and often mutations in PTCH. In addition, somatic mutations in 'smoothened' (SMOH; 601500), another protein in the hedgehog pathway, occur in sporadic BCCs. The downstream molecule GLI1 (165220) is known to mediate the biologic effect of the hedgehog pathway and is itself upregulated in all BCCs. Gli1 can drive the production of BCCs in the mouse when overexpressed in the epidermis. Xie et al. (2001) showed that GLI1 can activate PDGFR-alpha and that functional upregulation of PDGFR-alpha by GLI1 is accompanied by activation of the Ras-ERK pathway, which is associated with cell proliferation. The relevance of this mechanism in vivo is supported by a high level of expression of PDGFR-alpha in BCCs in mice and humans. From these and other observations, Xie et al. (2001) concluded that increased expression of the PDGFR-alpha gene may be an important mechanism by which mutations in the hedgehog pathway cause BCCs.
Ikuno and Kazlauskas (2002) studied the role of transforming growth factor-beta (TGFB1; 190180) in the tractional retinal detachments of proliferative vitreoretinopathy. Their results showed that vitreous promoted cellular contraction, that TGFB1 was the major factor responsible, and that at least a portion of the TGFB1-dependent contraction proceeded through PDGFRA. Thus, they concluded that PDGFRA is responsible for mediating cellular contraction of multiple growth factors: TGFB1 and members of the PDGF family.
Di Pasquale et al. (2003) characterized 43 cell lines as permissive or nonpermissive for adeno-associated virus type 5 (AAV-5) transduction and compared the gene expression profiles derived from cDNA microarray analyses of those cell lines. A statistically significant correlation was observed between expression of PDGFR-alpha and AAV-5 transduction. Subsequent experiments confirmed the role of PDGFR-alpha and PDGFR-beta (PDGFRB; 173410) as receptors for AAV-5. Di Pasquale et al. (2003) also noted that the tropism of AAV-5 in vivo correlated with the expression pattern of PDGFR-alpha.
Proliferative vitreoretinopathy (PVR; see 193235) is a disorder characterized by the formation of cellular membranes on both surfaces of the retina and within the vitreous cavity. Lei et al. (2007) noted that in the rabbit model of the disease, PDGFRA is dramatically more capable of promoting PVR than is the closely related PDGFRB. To test the ligand hypothesis (i.e., that this phenomenon can be explained by a predominance of PDGFRA-specific ligands), Lei et al. (2007) studied the profile of PDGF ligands expressed by cells that induced PVR and assessed the relevance of the rabbit model to the clinical setting. PDGF isoforms that activated PDGFRA predominated in all samples tested, with PDGFC (608452) being the predominant isoform. The profile of PDGF isoforms observed in the rabbit model accurately reflected the clinical specimens from patients with PVR.
Soroceanu et al. (2008) demonstrated that PDGFRA is specifically phosphorylated by both laboratory and clinical isolates of human cytomegalovirus (CMV) in various human cell types, resulting in activation of the phosphoinositide-3-kinase (PI(3)K; see 601232) signaling pathway. Upon stimulation by human CMV, tyrosine-phosphorylated PDGFRA associated with the p85 regulatory subunit of PI(3)K (PIK3R1; 171833) and induced protein kinase B (see AKT1, 164730) phosphorylation, similar to the genuine ligand, PDGF-AA. Cells in which PDGFRA was genetically deleted or functionally blocked were nonpermissive to human CMV entry, viral gene expression, or infectious virus production. Reintroducing the human PDGFRA gene into knockout cells restored susceptibility to viral entry and essential viral gene expression. Blockade of receptor function with a humanized PDGFRA blocking antibody (IMC-3G3) or targeted inhibition of its kinase activity with a small molecule (Gleevec) completely inhibited human CMV viral internalization and gene expression in human epithelial, endothelial, and fibroblast cells. Viral entry in cells harboring endogenous PDGFRA was competitively inhibited by pretreatment with PDGF-AA. Soroceanu et al. (2008) further demonstrated that human CMV glycoprotein B directly interacts with PDGFRA, resulting in receptor tyrosine phosphorylation, and that glycoprotein B neutralizing antibodies inhibit human CMV-induced PDGFRA phosphorylation. The authors concluded that PDGFRA is a critical receptor required for human CMV infection, and thus a target for novel antiviral therapies.
Chen et al. (2011) showed that PDGFR signaling controls age-dependent beta cell proliferation in mouse and human pancreatic islets. With age, declining beta cell Pdgfr levels were accompanied by reductions in beta cell Ezh2 (601573) levels and beta cell replication. Conditional inactivation of the Pdgfra gene in beta cells accelerated these changes, preventing mouse neonatal beta cell expansion and adult beta cell regeneration. Targeted human PDGFRA activation in mouse beta cells stimulated Erk1/2 (601795, 176948) phosphorylation, leading to Ezh2-dependent expansion of adult beta cells. Adult human islets lack PDGF signaling competence, but exposure of juvenile human islets to PDGF-AA stimulated beta cell proliferation.
Mueller et al. (2016) showed in mice that PDGFR-alpha signaling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. FAPs produce multiple transcriptional variants of Pdgfra with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signaling and to prevent FAP overactivation. Moreover, increasing the expression of this isoform limits fibrosis in vivo in mice, suggesting both biologic relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations.
By Western blot, immunofluorescence, and confocal microscopy analyses, Charbonneau et al. (2016) demonstrated that the receptor tyrosine kinase PDGFR was specifically upregulated in rheumatoid arthritis (RA; 180300) synoviocytes and synovial tissues. PDGFR activation involved TGFB-induced upregulation of PDGFB (190040) mediated by the TGFBR1 (190181)/SMAD (see 601366) and PI3K (see 171834)/AKT pathways. Charbonneau et al. (2016) proposed that an overreactive TGFB/PDGFB/PDGFR pathway is involved in synoviocyte-driven extracellular matrix degradation in RA.
PDGFRA/FIP1L1 Fusion Protein
Stover et al. (2006) stated that several variations of the FIP1L1/PDGFRA fusion protein have been identified in clinical studies of HES and systemic mast cell disease, but in all disease-associated cases, the autoinhibitory juxtamembrane (JM) domain of PDGFRA has been disrupted. By examining the kinase activity of several FIP1L1/PDGFRA fusion proteins, they determined that the FIP1L1 sequence was completely dispensable for PDGFRA activation in vitro and in vivo. On the other hand, N-terminal truncation of PDGFRA between 2 conserved tryptophan residues in the JM region was required for kinase activation and transforming potential of FIP1L1/PDGFRA. The presence of a complete JM domain in the FIP1L1/PDGFRA fusion protein inhibited activation of PDGFRA kinase activity.
Gene Family
The PDGFR2 gene is located on chromosome 4q11-q12 (Disteche et al., 1989; Gronwald et al., 1990). The KIT oncogene (164920), another member of the PDGF growth factor receptor subfamily, is located in the same region of chromosome 4 (Stenman et al., 1989). PDGFR1 and CSF1R (164770) are also membrane-spanning growth factor receptors with tyrosine kinase activity. The PDGFR1 and CSF1R genes appear to have evolved from a common ancestral gene by gene duplication, inasmuch as these 2 genes are tandemly linked on chromosome 5 (Roberts et al., 1988). They are oriented head-to-tail with the 5-prime exon of FMS located only 500 bp from the last 3-prime exon of PDGFRB. An analogous situation may exist for the PDGFR2 and KIT genes on chromosome 4. From an evolutionary point of view, it is possible that the distribution of these 4 loci, PDGFR2, KIT, PDGFR1, and FMS, on chromosomes 4 and 5 is a result of gene duplication and chromosome doubling (tetraploidization).
Mapping
Matsui et al. (1989) localized the PDGFRA gene to 4q11-q12 by in situ hybridization.
Disteche et al. (1989) and Gronwald et al. (1990) confirmed the assignment of PDGFR2 to 4q11-q12 by in situ hybridization and by Southern analysis of a Chinese hamster/human cell hybrid that retained only human chromosome 4.
Hsieh et al. (1991) assigned the PDGFRA gene to 4q11-q21 in the human and to chromosome 5 in the mouse by analysis of somatic cell hybrids. The Pdgfra locus is closely linked to the Kit oncogene on mouse chromosome 5, in a region syntenic to the homologous genes in the human on chromosome 4. The mouse 'Patched' (Ptch) mutation, which causes a spotted phenotype, is caused by a deletion in the Pdgfra gene (Stephenson et al., 1991; Smith et al., 1991). (The closely linked Kit gene in the mouse is the site of the dominant spotting (W) mutation.)
Molecular Genetics
Gastrointestinal Stromal Tumors
Heinrich et al. (2003) found intragenic activation somatic mutations in the PDGFRA gene (see, e.g., 173490.0001-173490.0007) in approximately 35% of gastrointestinal stromal tumors (GIST; 606764).
In affected members of a French family with autosomal dominant inheritance of gastrointestinal stromal tumors, Chompret et al. (2004) identified a heterozygous germline mutation in the PDGFRA gene (D846Y; 173490.0009).
De Raedt et al. (2006) identified a heterozygous germline mutation in the PDGFRA gene (Y555C; 173490.0010) in 3 affected sisters from a family with dominant inheritance of GISTs. The family had previously been reported by Verhest et al. (1988) and Heimann et al. (1988).
Associations Pending Confirmation
Tumors
De Bustos et al. (2005) examined the PDGFRA gene promoter haplotype in brain tumor patients and found a significant overrepresentation of the H2-delta haplotype in patients with primitive neuroectodermal tumors (10-fold) and ependymomas (6.5-fold). They also noted that the H2-delta haplotype specifically disrupted binding of the transcription factor ZNF148 (601897) and suggested that the ZNF148/PDGFRA pathway has a functional role in the pathogenesis of these tumors.
By sequencing the exons encoding the kinase domains of 20 receptor tyrosine kinases in 19 glioblastomas, Rand et al. (2005) identified 2 somatic mutations in the FGFR1 gene (136350) in separate tumors and a somatic mutation in the PDGFRA gene in another tumor. The PDGFRA mutation was a 2-bp deletion in the terminal exon 23 that led to a frameshift and substitution of amino acids 1049 to 1089 with a single histidine.
Neural Tube Defects
Mouse models indicated that deregulated expression of the Pdgfra gene causes congenital neural tube defects (NTDs), and mutant forms of PAX1 that have been associated with NTDs caused deregulated activation of the human PDGFRA promoter. Joosten et al. (2001) identified 5 different haplotypes in the human PDGFRA promoter, of which the 2 most abundant, designated H1 and H2-alpha, differ in at least 6 polymorphic sites. In a transient transfection assay in human bone cells, the 5 haplotypes differed strongly in their ability to enhance reporter gene activity. In a group of patients with sporadic spina bifida, haplotypes with low transcriptional activity, including H1, were underrepresented, whereas those with high transcriptional activity, including H2-alpha, were overrepresented. When testing for haplotype combinations, H1 homozygotes were fully absent from the group of sporadic patients, whereas H1/H2-alpha heterozygotes were overrepresented in the group of both sporadic and familial spina bifida patients, but strongly underrepresented in unrelated controls. The data indicated that specific combinations of naturally occurring PDGFRA promoter haplotypes strongly affect NTD genesis.
Isolated Cleft Palate
By sequencing the entire coding region and the 708-bp 3-prime untranslated region (UTR) of the PDGFRA gene in 102 unrelated Thai patients with nonsyndromic cleft palate (CP), Rattanasopha et al. (2012) identified 7 novel single basepair substitutions in 9 (8.8%) of 102 patients compared with 5 (1%) of 500 ethnically matched unaffected controls (2-tailed P-value less than 0.0001). There were 4 missense mutations detected in the coding regions (see, e.g., 173490.0011-173490.0013) and 3 in the 3-prime UTR, including 34G-A. Comparing the frequency of all identified variants between individuals with CP and the unaffected controls, these 4 variants had a significantly higher frequency in CP patients than in the unaffected controls (P less than 0.05). Functional analysis by the luciferase assay revealed that the 34G-A transition in the 3-prime UTR could significantly repress luciferase activity compared with that of the wildtype in the presence of miR-140.
Animal Model
Helwig et al. (1995) reported that mice who are doubly heterozygous for the mutants 'undulated' and 'Patched' have a phenotype reminiscent of an extreme form of spina bifida occulta (182940) in humans. The unexpected phenotype in double-mutant and not in single-mutant mice showed that novel congenital anomalies such as spina bifida can result from interaction between products of independently segregating loci. This is an example of digenic inheritance. (The 'undulated' mutation is situated in the mouse Pax1 gene.)
Klinghoffer et al. (2001) created 2 complementary lines of knockin mice in which the intracellular signaling domains of one PDGFR had been removed and replaced by those of the other PDGFR. While both lines demonstrated substantial rescue of normal development, substitution of the Pdgfrb signaling domains with those of Pdgfra resulted in varying degrees of vascular disease.
Bleyl et al. (2007) observed that the homozygous Pdgfra-null mouse had posterolateral diaphragmatic defects and concluded that the mouse is a model for human congenital diaphragmatic hernia (see 142340).
Su et al. (2008) demonstrated that intraventricular administration of tPA (TPA; 173370) in mice increased cerebrovascular permeability via activation of Pdgfcc (see 608452) and Pdgfra. Morphologic changes were observed primarily in arterioles. Immunohistochemical studies showed that Pdgfcc was localized to arterioles in the cortex, striatum, and hippocampus, as well as additional brain regions, and closely resembled tissue distribution of tPA. The Pdgfra receptor was located primarily on perivascular astrocytes associated with arterioles. In a mouse model of ischemic stroke with tPA administration, treatment with the PDGFR-alpha inhibitor imatinib resulted in decreased cerebrovascular permeability and reduced lesion volume. Su et al. (2008) suggested that the known association of hemorrhagic complications in some patients with ischemic stroke treated with tPA may be due in part to the activation of PDGFCC and its receptor by therapeutic tPA. The findings also indicated that PDGF signaling regulates blood-brain barrier permeability.
Total anomalous pulmonary venous return (TAPVR; 106700) is a congenital heart defect inherited via complex genetic and/or environmental factors. In gene expression studies in mouse and chick embryos for both the Pdgfra receptor and its ligand, Pdgfa, Bleyl et al. (2010) showed temporal and spatial patterns consistent with a role in pulmonary vein development. Loss of PDGFRA function in both chick and mouse embryos caused TAPVR with low penetrance (approximately 7%), reminiscent of that observed in human TAPVR kindreds. Intermediate inflow tract anomalies occurred in a higher percentage of embryos (approximately 30%), suggesting that TAPVR may occur at one end of a spectrum of defects.
ALLELIC VARIANTS 13 Selected Examples):
.0001 GASTROINTESTINAL STROMAL TUMOR, SOMATIC
In 8 gastrointestinal stromal tumors (GIST; 606764), Heinrich et al. (2003) identified an asp-to-val mutation at codon 842 (D842V) in exon 18 of the PDGFRA gene, encoding the activation loop. The mutation was limited to the tumor and was not found in genomic DNA from any of the affected individuals.
Using in vitro functional expression studies, De Raedt et al. (2006) demonstrated that the D842V mutation resulted in autophosphorylation and activation of the receptor, as well as IL3 (147740)-independent growth. The D842V mutant protein was not sensitive to imatinib inhibition.
.0002 GASTROINTESTINAL STROMAL TUMOR, SOMATIC
In the tumor but not genomic DNA of a patient with gastrointestinal stromal tumor (606764), Heinrich et al. (2003) identified a 4-amino acid deletion in exon 18 of the PDGFRA gene.
.0003 GASTROINTESTINAL STROMAL TUMOR, SOMATIC
In the tumor but not genomic DNA of a patient with gastrointestinal stromal tumor (606764), Heinrich et al. (2003) identified a 4-amino acid deletion in the activation loop of PDGFRA, encoded by exon 18 of the gene.
.0004 GASTROINTESTINAL STROMAL TUMOR, SOMATIC
In the tumor but not genomic DNA of a patient with gastrointestinal stromal tumor (606764), Heinrich et al. (2003) identified a somatic mutation in exon 12 of the PDGFRA gene, resulting in a val561-to-asp substitution (V561D) in the juxtamembrane domain.
Pasini et al. (2007) identified a heterozygous germline T-to-A transversion in the PDGFRA resulting in a V561D substitution in a woman with GISTs and other mesenchymal tumors. She developed intestinal obstruction at age 32 years and was found to have multiple mesenchymal fibroid intestinal tumors. Tumor tissue showed multiple secondary genetic changes, including loss of heterozygosity of several chromosomal regions such as 14q. Of note, the patient had a history of a duodenal lipoma, which had not previously been reported in patients with GISTs.
.0005 GASTROINTESTINAL STROMAL TUMOR, SOMATIC
In a tumor but not genomic DNA of a patient with gastrointestinal stromal tumor (606764), Heinrich et al. (2003) identified the insertion of 2 amino acids at codons 561 and 562 in exon 12 of the PDGFRA gene, which encodes the juxtamembrane domain.
.0006 GASTROINTESTINAL STROMAL TUMOR, SOMATIC
In a tumor but not genomic DNA of a patient with gastrointestinal stromal tumor (606764), Heinrich et al. (2003) identified a 5-amino acid deletion of codons 560-564 in exon 12 of the PDGFRA gene, which encodes the juxtamembrane domain.
.0007 GASTROINTESTINAL STROMAL TUMOR, SOMATIC
In a tumor but not genomic DNA of a patient with gastrointestinal stromal tumor (606764), Heinrich et al. (2003) identified a 5-amino acid deletion in exon 12 of the PDGFRA gene, which encodes the juxtamembrane domain.
.0008 HYPEREOSINOPHILIC SYNDROME, IDIOPATHIC, RESISTANT TO IMATINIB
In a patient with idiopathic hypereosinophilic syndrome (607685) caused by a fusion gene formed of the first 233 amino acids of FIP1L1 (607686) to the last 523 amino acids of PDGFRA, Cools et al. (2003) noted that the resulting constitutively activated tyrosine kinase was inhibited by imatinib, causing clinical remission. Relapse was found to correlate with the appearance of a thr674-to-ile (T674I) mutation in PDGFRA that conferred resistance to imatinib.
.0009 GASTROINTESTINAL STROMAL TUMOR, FAMILIAL
In affected members of a French family with autosomal dominant inheritance of GISTs (606764), Chompret et al. (2004) identified a heterozygous 2675G-T transversion in the PDGFRA gene, resulting in an asp846-to-tyr (D846Y) substitution in the putative tyrosine kinase domain.
.0010 GASTROINTESTINAL STROMAL TUMOR, FAMILIAL
In 3 affected sisters from a family with dominant inheritance of GISTs (606764), De Raedt et al. (2006) identified a heterozygous 1664A-G transition in the PDGFRA gene, resulting in a tyr555-to-cys (Y555C) substitution in the juxtamembrane domain. In vitro functional expression studies showed that the Y555C mutation leads to autophosphorylation and activation of the receptor. The mutant protein was sensitive to imatinib inhibition. The family had previously been reported by Verhest et al. (1988) and Heimann et al. (1988).
.0011 VARIANT OF UNKNOWN SIGNIFICANCE
This variant is classified as a variant of unknown significance because its contribution to isolated cleft palate (CP; see 119540) has not been confirmed.
Rattanasopha et al. (2012) sequenced the entire coding region and the 708-bp 3-prime UTR of the PDGFRA gene in 102 unrelated Thai patients with nonsyndromic CP. In 3 patients and in 1 of 500 ethnically matched unaffected controls, they identified a 1202C-A transversion resulting in an ala401-to-asp (A401D) substitution.
.0012 VARIANT OF UNKNOWN SIGNIFICANCE
This variant is classified as a variant of unknown significance because its contribution to isolated cleft palate (CP; see 119540) has not been confirmed.
Rattanasopha et al. (2012) sequenced the entire coding region and the 708-bp 3-prime UTR of the PDGFRA gene in 102 unrelated Thai patients with nonsyndromic CP. In 1 patient, they identified a heterozygous 1631T-C transition resulting in a val544-to-ala (V544A) substitution. This variant was not found in 500 ethnically matched controls.
.0013 VARIANT OF UNKNOWN SIGNIFICANCE
This variant is classified as a variant of unknown significance because its contribution to isolated cleft palate (CP; see 119540) has not been confirmed.
Rattanasopha et al. (2012) sequenced the entire coding region and the 708-bp 3-prime UTR of the PDGFRA gene in 102 unrelated Thai patients with nonsyndromic CP. In 1 patient, they identified a heterozygous 3155C-T transition resulting in a thr1052-to-met substitution. This variant was not found in 500 ethnically matched controls.
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Patricia A. Hartz - updated : 01/27/2017
Ada Hamosh - updated : 01/10/2017
Nara Sobreira - updated : 1/24/2013
Ada Hamosh - updated : 11/29/2011
George E. Tiller - updated : 11/14/2011
Ada Hamosh - updated : 10/2/2008
Cassandra L. Kniffin - updated : 7/22/2008
John A. Phillips, III - updated : 4/4/2008
Cassandra L. Kniffin - updated : 4/2/2008
Jane Kelly - updated : 11/29/2007
Kelly A. Przylepa - updated : 10/1/2007
Paul J. Converse - updated : 5/17/2007
Patricia A. Hartz - updated : 7/6/2006
Marla J. F. O'Neill - updated : 3/21/2005
Ada Hamosh - updated : 9/23/2003
Victor A. McKusick - updated : 4/9/2003
George E. Tiller - updated : 2/25/2003
Ada Hamosh - updated : 2/13/2003
Jane Kelly - updated : 7/9/2002
Victor A. McKusick - updated : 9/27/2001
Carol A. Bocchini - updated : 5/24/2001
Stylianos E. Antonarakis - updated : 3/12/2001
Victor A. McKusick - updated : 1/25/2001
Victor A. McKusick - updated : 12/10/1998
Alan F. Scott - updated : 1/15/1996
mgross : 01/27/2017
carol : 01/11/2017
alopez : 01/10/2017
carol : 09/04/2014
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carol : 1/24/2013
alopez : 12/1/2011
terry : 11/29/2011
carol : 11/17/2011
terry : 11/14/2011
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alopez : 10/6/2008
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ckniffin : 7/22/2008
carol : 4/4/2008
ckniffin : 4/2/2008
carol : 11/29/2007
carol : 11/13/2007
terry : 10/1/2007
mgross : 5/17/2007
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terry : 7/6/2006
wwang : 3/21/2005
alopez : 11/17/2003
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carol : 5/28/2003
tkritzer : 4/11/2003
tkritzer : 4/11/2003
terry : 4/9/2003
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alopez : 2/19/2003
alopez : 2/19/2003
terry : 2/13/2003
mgross : 7/9/2002
mcapotos : 10/29/2001
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carol : 5/24/2001
mgross : 3/12/2001
alopez : 1/29/2001
terry : 1/25/2001
mgross : 3/17/1999
carol : 12/16/1998
terry : 12/10/1998
jenny : 7/9/1997
terry : 4/17/1996
mark : 1/15/1996
mark : 8/31/1995
carol : 10/20/1992
supermim : 3/16/1992
carol : 3/2/1992
carol : 8/20/1991
carol : 6/19/1991