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| Hereditary Erythrocytosis v2.5 | PKLR |
Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from 'both mono- and biallelic' to 'monoallelic' only. Limited evidence but historic reports linked heterozygous variants in the PKLR gene to elevation of red cell ATP levels, accompanied by elevated red cell pyruvate kinase activity and mild erythrocytosis. Patients were asymptomatic and no recent cases have been published therefore Red rating is appropriate (PMIDs: 9090535; 4160306; 14300761; 7426754). Biallelic variants cause pyruvate kinase deficiency which results in nonspherocytic hemolytic anemia rather than erythrocytosis. |
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| Hereditary Erythrocytosis v1.41 | SLC30A10 | Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by external reviewer Dmitrijs Rots. There is enough evidence to promote this gene to Green at the next GMS panel update. All affected individuals reported to date (>3) had polycythemia at the time of diagnosis, which can precede the onset of neurologic manifestations and therefore it is worth including SLC30A10 on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis v1.36 | BPGM |
Arina Puzriakova Added comment: Comment on mode of inheritance: Three patients described in literature with biallelic variants (PMID: 1421379; 15054810; 33216349) and 2 with heterozygous variants (PMID: 25015942; 27651169) in the BPGM gene. Heterozygous variants in some cases may cause milder erythrocytosis due to partial BPGM deficiency. Of the four individuals (2 homo, 2 het) identified in the paper reviewed by Dmitrijs Rots (PMID: 29790589), three variants were classified VUS and the other had been previously reported and therefore these cases could not be included. Although the number of monoallelic cases does not reach the threshold for inclusion, the evidence supports an association with erythrocytosis. To reduce risk of potentially missed diagnoses the MOI may be considered for update from 'biallelic' to 'both mono- and biallelic' but this will be flagged for further GMS review. In any case, BPGM should be promoted to Green at the next GMS panel update with the respective MOI based on the decision of the expert working group. |
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| Hereditary Erythrocytosis v1.35 | SLC30A10 |
Dmitrijs Rots gene: SLC30A10 was added gene: SLC30A10 was added to Hereditary Erythrocytosis. Sources: Literature Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC30A10 were set to PMID: 22341971; 22341972 Phenotypes for gene: SLC30A10 were set to Erythrocytosis; Polycytemia; Hypermanganesemia; Parkinsonism; Dystonia; Liver disease Review for gene: SLC30A10 was set to GREEN Added comment: In 6 individuals from two families and 14 individuals from 8 families reported in in 22341971 and 22341972, respectively - all have erythrocytosis/polycytemia. Sources: Literature |
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| Hereditary Erythrocytosis v1.26 | EPOR | Arina Puzriakova Phenotypes for gene: EPOR were changed from Polcythaemia; erythrocytosis; Familial Erythrocytosis to [Erythrocytosis, familial, 1], OMIM:133100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis v1.13 | SH2B3 | Sarah Leigh Added comment: Comment on list classification: An amber rating has been given to SH2B3, as only somatic variants in this gene have been reported to be associated with Erythrocytosis, somatic 133100. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis v1.12 | JAK2 | Sarah Leigh Added comment: Comment on list classification: An amber rating has been given to JAK2, as only somatic variants in this gene have been reported to be associated with Erythrocytosis, somatic 133100. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis v1.10 | BPGM | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 4 variants reported in 3 unrelated cases, although two of the cases are biallelic (PMID 25015942, 15054810), one case appears to monoallelic (PMID 25015942). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis | EPOR | Olivia Niblock marked EPOR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis | EPOR | Olivia Niblock classified EPOR as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis | EPOR | Olivia Niblock commented on EPOR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis | EPOR | Daniel Gale reviewed EPOR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis | EPOR | Ellen McDonagh added EPOR to panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Erythrocytosis | EPOR | Ellen McDonagh reviewed EPOR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||