Respiratory ciliopathies including non-CF bronchiectasis
Gene: PIK3CDComment on phenotypes: Phenotype added based on external expert review and evidence from OMIMCreated: 16 Jan 2019, 2:45 p.m.
Comment on list classification: Upgraded to green based on review by Ian Berry.Created: 16 Jan 2019, 2:42 p.m.
PMID 29556229; gain-of-function mutations cause a form of primary immunodeficiency which frequently results in bronchiectasis with limited additional immunological findings.
Expert review by Dr Sinisa Savic (Clinical Immunologist) and Dr Daniel Peckham (Respiratory Physician), bronchiectasis expert team from Leeds.Created: 11 Jan 2019, 4:40 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: agreed there enough evidence to rate this gene GreenCreated: 21 Jan 2019, 5:27 p.m.
Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: PIK3CD; Suggested initial gene rating: Amber; Evidence for inclusion: Immunodeficiency 14 on OMIM; recurrent respiratory infections.; Evidence for exclusion: Need to include some/all of CVID/PID genes, nothing special about this one.; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none givenCreated: 5 Dec 2018, 1:54 p.m.
Activated PI3K-δ Syndrome (APDS), a Primary Immunodeficiency associated with a dominant gain-of-function mutation E1021K in the p110δ protein, the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), encoded by the PIK3CD gene. We found E1021K in 17 patients from seven unrelated families, but not among 3,346 healthy subjects. APDS was characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased IgM and reduced IgG2 levels in serumCreated: 17 Oct 2015, 7:08 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Other
Comment on list classification: Originally a red gene, however has a green expert review and multiple cases reported in OMIM. Several different missense variants have been reported which have a gain-of-function effect, which will be considered tier 2.Created: 10 May 2016, 9:49 a.m.
"PI3Kinase delta activating mutation" was submitted by an expert. The HGNC approved symbol for this gene was curated as PIK3CD, and mode of pathogenicity was added as gain of function to capture the information from the expert.Created: 8 Jul 2015, 10:28 a.m.
Phenotypes for gene: PIK3CD were changed from Immunodeficiency 14, 615513; Bronchiectasis to Immunodeficiency 14A, autosomal dominant, OMIM:615513; Bronchiectasis
Phenotypes for gene: PIK3CD were changed from to Immunodeficiency 14, 615513; Bronchiectasis
Mode of pathogenicity for gene: PIK3CD was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: PIK3CD were set to
Gene: pik3cd has been classified as Green List (High Evidence).
Mode of inheritance for gene: PIK3CD was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Source Expert Review Amber was added to PIK3CD. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
gene: PIK3CD was added gene: PIK3CD was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS Mode of inheritance for gene: PIK3CD was set to