Respiratory ciliopathies including non-CF bronchiectasis

Gene: PIK3CD

Comment on phenotypes: Phenotype added based on external expert review and evidence from OMIM

Created: 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.

Green List (high evidence)

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

• PMID: 29556229

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

I don't know

From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: agreed there enough evidence to rate this gene Green

Created: 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 given

Created: 5 Dec 2018, 1:54 p.m.

Green List (high evidence)

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 serum

Created: 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.