Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: POLA1
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 14 Oct 2020, 1:40 p.m. | Last Modified: 14 Oct 2020, 1:40 p.m.
Panel Version: 2.294
The following PubMed IDs were added to entity POLA1: 15804299;6794369. These publications have been associated with OMIM phenotype MIM#301220, which is listed for this entity, by the autoinflammation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Comment on phenotypes: Added OMIM phenotypeCreated: 5 Jul 2018, 4:39 p.m.
Comment on publications: Added publication reporting cases of variants in POLA1Created: 5 Jul 2018, 4:39 p.m.
Comment on list classification: Probable disease causing mutation found in more than 3 families. Segregation pattern following an X-linked pattern of inheritance is seen.Created: 5 Jul 2018, 4:38 p.m.
In OMIM this gene is associated with Pigmentary disorder, reticulate, with systemic manifestations, X-linked. OMIM reports that in affected members of 12 unrelated families with X-linked reticulate pigmentary disorder (PDR; 301220), Starokadomskyy et al. (2016) (PMID: 27019227) identified a hemizygous (in males) or heterozygous (in females) intronic mutation in the POLA1 gene resulting the introduction of a novel exon. All affected individuals carried the same mutation, which was initially identified by whole-genome sequencing of 4 probands. Haplotype analysis showed that 2 of the families shared a common founder, but others gained the mutation independently, including at lease 1 de novo case. Patient fibroblasts and lymphoblastoid cells showed aberrant splicing and a decrease in POLA1 protein levels to about 35% that of controls.Created: 5 Jul 2018, 4:36 p.m.
Publications
Very strong genetic evidence that a recurrent intronic variant causes this disorder in multiple unrelated kindredsCreated: 30 Jun 2018, 5:11 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
X-linked reticulate pigmentary disorder; x-linked cutaneous amyloidosis with systemic features
Publications
Gene: pola1 has been classified as Green List (High Evidence).
Source Other was added to POLA1. Publications for gene POLA1 were updated from 27019227 to 27019227; 6794369; 15804299 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to POLA1.
Source North West GLH was added to POLA1.
Source London North GLH was added to POLA1.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Gene: pola1 has been classified as Green List (High Evidence).
Phenotypes for gene: POLA1 were set to Hyperpigmentation, characteristic facies, lung and GI involvement; Autoinflammatory Disorders; Pigmentary disorder, reticulate, with systemic manifestations, X-linked 301220; X-linked reticulate pigmentary disorder; x-linked cutaneous amyloidosis with systemic features
Phenotypes for gene: POLA1 were set to Hyperpigmentation, characteristic facies, lung and GI involvement; Autoinflammatory Disorders; Pigmentary disorder, reticulate, with systemic manifestations, X-linked 301220
Publications for gene: POLA1 were set to 27019227
Mode of inheritance for gene: POLA1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Gene: pola1 has been classified as Green List (High Evidence).
Phenotypes for gene POLA1 were set to Hyperpigmentation, characteristic facies, lung and GI involvement, Autoinflammatory Disorders
POLA1 was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018
POLA1 was created by Louise Daugherty