Cystic kidney disease

Gene: FLCN

Amber List (moderate evidence)

FLCN (folliculin)
EnsemblGeneIds (GRCh38): ENSG00000154803
EnsemblGeneIds (GRCh37): ENSG00000154803
OMIM: 607273, Gene2Phenotype
FLCN is in 12 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting from grey to amber, with a recommendation for green rating at the next GMS review.
Created: 29 Apr 2021, 10:44 p.m. | Last Modified: 29 Apr 2021, 10:44 p.m.
Panel Version: 2.26
Associated with Birt-Hogg-Dube syndrome #135150 (AD) in OMIM.

PMID:19785621 - Kluger et al 2010 - report the clinical features 22 patients from 10 unrelated families with BHDS and a confirmed FLCN (previously BHD) germline mutation (FLCN only sequenced). 5 different variants were identified (frameshift, nonsense, splice site, missense and translation initiation site). Renal cysts were found in in 10 patients (45%). Skin and lung phenotypic features were also observed in patients. 2 patients were considered carriers without any symptoms to date.

PMID: 31266032 - Torricelli et al 2019 - looked at patients with spontaneous pneumothorax and a family history of this condition. Pulmonary cysts were found in all patients with a FLCN-positive genetic test. Renal cysts were found in 4/13 (31%) patients.
Created: 29 Apr 2021, 10:43 p.m. | Last Modified: 29 Apr 2021, 10:43 p.m.
Panel Version: 2.25

Daniel Gale (UCL)

Green List (high evidence)

Birt Hogg Dube syndrome (caused by variants in FLCN) is frequently associated with multiple renal cysts, without renal enlargement or progressive CKD. Previous published data indicate simple renal cysts present in 31-45% (PMID: 31266032;19785621) of patients with BHD and audit of 20 patients I follow up revealed simple renal cysts in 11 (multiple in 9 of these individuals) i.e. similar to the literature. Therefore BHD should be considered in the differential diagnosis of multiple renal cysts (without renal enlargement).
Sources: Literature, Expert Review
Created: 22 Mar 2021, 12:05 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Birt-Hogg-Dube syndrome, OMIM:135150
  • renal cysts
  • cutaneous fibrofolliculoma
  • pneumothorax
  • pulmonary cysts
  • renal cell carcinoma
  • renal oncocytoma
Tags
Q2_21_rating
OMIM
607273
Clinvar variants
Variants in FLCN
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

29 Apr 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: flcn has been classified as Amber List (Moderate Evidence).

29 Apr 2021, Gel status: 0

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: FLCN.

29 Apr 2021, Gel status: 0

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: FLCN were set to PMID: 19785621; 31266032

29 Apr 2021, Gel status: 0

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: FLCN were changed from renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma to Birt-Hogg-Dube syndrome, OMIM:135150; renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma

22 Mar 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Daniel Gale (UCL)

gene: FLCN was added gene: FLCN was added to Cystic kidney disease. Sources: Literature,Expert Review Mode of inheritance for gene: FLCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FLCN were set to PMID: 19785621; 31266032 Phenotypes for gene: FLCN were set to renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma Penetrance for gene: FLCN were set to Incomplete Review for gene: FLCN was set to GREEN