Respiratory ciliopathies including non-CF bronchiectasis
Gene: RPGR
Although few cases of PCD associated with RPGR variants have been published, the PCD diagnostic centre at University Hospital Southampton has diagnosed 5 cases of PCD where RPGR variants have been judged to be the cause of disease. 4 cases have stop gains in RPGR, 3 of whom had PCD diagnosed before eye disease and 1 of whom is an adult whose wet cough and rhinitis started in very early childhood before eye symptoms, but was diagnosed with RP before PCD (due to late referral for PCD rather than lack of symptoms). i.e. in all cases lung disease preceded eye disease. 1 case has a pathogenic missense mutation and is an adult who only has PCD, no eye disease. I am submitting this review as a researcher who works closely with the diagnostic service at UHS and Wessex Clinical Genetics Lab. The fact that RPGR has been downgraded to Amber was raised at our recent PCD genetics MDT and Prof Jane Lucas, who leads the diagnostic service at UHS asked me to submit a review to provide support for this gene being a 'Green' gene.
Created: 25 Jan 2021, 3:56 p.m. | Last Modified: 28 Jan 2021, 1 p.m.
Panel Version: 1.42
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
primary ciliary dyskinesia; non-CF bronchiectasis
Publications
Mode of pathogenicity
Other
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 11:15 a.m. | Last Modified: 8 Mar 2022, 11:15 a.m.
Panel Version: 1.55
This gene is associated with an appropriate phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be promoted to Green status at the next review.Created: 2 Dec 2020, 1:57 p.m. | Last Modified: 2 Dec 2020, 1:57 p.m.
Panel Version: 1.29
Comment on publications: PMID: 22888088 and 14627685 are extra casesCreated: 2 Dec 2020, 1:56 p.m. | Last Modified: 2 Dec 2020, 1:56 p.m.
Panel Version: 1.29
Three unrelated families reported where males have sinorespiratory infections in addition to RP.Created: 25 May 2020, 7:34 a.m. | Last Modified: 25 May 2020, 7:34 a.m.
Panel Version: 1.7
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, MIM# 300455
Publications
Variants in this GENE are reported as part of current diagnostic practice
From GMS Respiratory Specialist Test Group webex call 18th Jan 2019; Agreed to keep Amber, not enough evidence to upgrade to Green. it was also felt that this might present with respiratory features before RP, however there are difficulties with coverage by NGSCreated: 21 Jan 2019, 5:24 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: RPGR; Suggested initial gene rating: Amber; Evidence for inclusion: XLRP can sometimes manifest with recurrent respiratory infections.; Evidence for exclusion: Syndromic, ocular manifestations main phenotype.; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): ORF15 difficult to sequence (repetitive region)Created: 5 Dec 2018, 1:54 p.m.
Phenotype not clealy relevant to isomerism. See expert review from Hannah Mitchison for rationale for inclusion on PCD panelCreated: 4 Jul 2017, 7:25 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Retinitis pigmentosa 3
Comment on list classification: Discussed in group at GEL and agreed to include due to phenotypic overlapCreated: 10 May 2016, 9:57 a.m.
Gene should be deleted - causes a primary ciliopathy;PCD is a motile ciliopathy, likely unrelated at a functional level.Created: 8 Dec 2015, 5:33 p.m.
Phenotypes
ciliopathies
UK mutations reported. OMIM does not seem to have picked up RPGR as an increasingly important cause of syndromic PCD syndromic cause. It is now clear that RPGR mutations can cause PCD+RP in a number of cases. (HM unpublished data and Bukowy-Bieryllo et al. Pediatr Pulmonol. 2013 Apr;48(4):352-63)Created: 8 Dec 2015, 4:25 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: RPGR.
Source Expert Review Green was added to RPGR. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag for-review tag was added to gene: RPGR.
Publications for gene: RPGR were set to 10094550; 12920075; 16055928
Phenotypes for gene: RPGR were changed from Ciliopathies to Ciliopathies; Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, OMIM:300455; primary ciliary dyskinesia-retinitis pigmentosa syndrome, MONDO:0010330
Publications for gene: RPGR were set to
Mode of inheritance for gene RPGR was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females Added phenotypes Ciliopathies for gene: RPGR
Source Expert Review Amber was added to RPGR. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
gene: RPGR was added gene: RPGR was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS Mode of inheritance for gene: RPGR was set to