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Mendeliome

Gene: PDGFRA

Green List (high evidence)

PDGFRA (platelet derived growth factor receptor alpha)
EnsemblGeneIds (GRCh38): ENSG00000134853
EnsemblGeneIds (GRCh37): ENSG00000134853
OMIM: 173490, Gene2Phenotype
PDGFRA is in 4 panels

2 reviews

Ain Roesley (Victorian Clinical Genetics Services)

Red List (low evidence)

1x family with AD coloboma

Also presented with global developmental delay, autistic behaviour, delayed gross motor development

zebrafish KO model
Created: 5 May 2022, 1:46 a.m. | Last Modified: 5 May 2022, 1:52 a.m.
Panel Version: 0.13795

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
coloboma MONDO#0001476, PDGFRA-related

Publications

Variants in this GENE are reported as part of current diagnostic practice

Krithika Murali (Victorian Clinical Genetics Services)

Green List (high evidence)

Six unrelated families reported with heterozygous germline variants associated with familial GIST and/or inflammatory fibroid polyps - IFP (benign lesions caused by excessive tissue proliferation and inflammatory cell infiltration into the lumen of the GI tract). Note that reported individuals diagnosed as adults. One individual reported with diagnosis of gastric mass/polyps age 22 (in 1977) raising the possibility of pre-symptomatic disease onset in adolescence. Green PanelApp England in the following panels: tumour predisposition - childhood onset; inherited predisposition to GIST; sarcoma cancer susceptibility.

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PMID 34107389 Hodan et al 2021 - report a 35 yo F with jejunal IFP and a heterozygous germline missense PDGFRA variant (c.1664A>G p.Y555C) . The variant segregated with 3 relatives with confirmed IFPs. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This variant was also reported in an unrelated family with multiple IFPs in 2006.

PMID 29486293 Manley et al 2018 - proband is a 50 yo M with multiple ileal intusussceptions and IFPs and GIST. Heterozygous D846V germline variant identified. Variant identified in daughter and 2 siblings. Coarser face, coarser skin, broader hands and feet, unexplained premature loss of teeth requiring dentures in their 40s described in relatives with the variant, no polyps or tumour identified in screened family members. Pdgfra +/K mutant mice recapitulated the human phenotype. Mice with the constitutively activated mutant PDGFRA shown to have diffuse expansion of the gastrointestinal submucosa, which exhibits an increased number of spindled fibroblast-like cells and marked collagen deposition. Mutant mice also develop intestinal polyps morphologically similar to IFPs. The Pdgfra +/K mice also exhibit thickened skin due to excess collagen deposition within the dermis and subcutaneous tissues.

PMID 25975287 Ricci et al 2015 - report a family with het germline P653L PDGFRA missense variant. The proband was a 67 yo M with multiple intra-abdominal GIST and gastric/colonic inflammatory fibroid polyps. Multiple adult relatives (youngest age 31) were diagnosed with IFPs/fibrous tumours with the variant segregating with disease.

PMID: 18670346 Carney et al 2008 and PMID: 17566086 Pasini et al 2007 - heterozygous germline PDGFRA mutation (V561D) in an individual with GIST and multiple polyps, diagnosed initially aged 22 with multiple GIST/polyps. No other relatives available for genotyping and no other significant family history reported.

PMID: 17087943 de Raedt et al 2006 - heterozygous PDGFRA(Y555C) variant reported in a family with multiple relatives affected by IFP, including one death from secondary bowel obstruction age 35.

PMID: 14699510 Chompret et al 2004 - Heterozygous c.2675G>T D846Y germline variant detected in a French family with 5 relatives developing adult-onset GIST, variant segregated with disease.

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Gain of function somatic variants associated with sporadic GIST. Somatic chromosomal rearrangements resulting in PDGFRA and FIP1L1 gene fusion associated with idiopathic hypereosinophilic syndrome.
Created: 26 Apr 2022, 2:50 a.m. | Last Modified: 26 Apr 2022, 3:12 a.m.
Panel Version: 0.13297

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial - MIM#175510

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial - MIM#175510
  • coloboma MONDO#0001476, PDGFRA-related
OMIM
173490
Clinvar variants
Variants in PDGFRA
Penetrance
None
Publications
Panels with this gene

History Filter Activity

5 May 2022, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: PDGFRA were changed from Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial - MIM#175510 to Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial - MIM#175510; coloboma MONDO#0001476, PDGFRA-related

5 May 2022, Gel status: 3

Set publications

Ain Roesley (Victorian Clinical Genetics Services)

Publications for gene: PDGFRA were set to 14699510; 17087943; 25975287; 29486293; 33449152; 34107389; 17566086; 18670346

26 Apr 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: pdgfra has been classified as Green List (High Evidence).

26 Apr 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PDGFRA were changed from to Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial - MIM#175510

26 Apr 2022, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PDGFRA were set to

26 Apr 2022, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: PDGFRA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: PDGFRA was added gene: PDGFRA was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: PDGFRA was set to Unknown