Cytopenia - NOT Fanconi anaemia

Gene: MPL

The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval. GMS reviewers also note that the monoallelic variants that were previously reported for this gene were associated with thrombocythaemia and not with thrombocytopenia.

Created: 1 Feb 2023, 8:15 a.m. | Last Modified: 1 Feb 2023, 8:19 a.m.

Panel Version: 2.3

Comment on mode of inheritance: The MOI on this panel should be reviewed at the next GMS panel update to determine the pertinent inheritance pattern (currently set to both AD/AR).

Biallelic variants cause thrombocytopenia (MIM# 604498) which in severe forms can present with pancytopenia, a phenotype that is within the scope of this panel. On the other hand, monoallelic variants are associated with thrombocythemia (MIM# 601977) which does not include features that may be relevant here. Therefore it may be appropriate to update the MOI to 'biallelic' only.

Created: 12 Apr 2022, 11:26 a.m. | Last Modified: 12 Apr 2022, 11:26 a.m.

Panel Version: 1.63

Green List (high evidence)

Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group.

Created: 18 Feb 2019, 2:55 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Thrombocytopenia, congenital amegakaryocytic, 604498

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.

Created: 14 Feb 2019, 5:39 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
604498 Thrombocytopenia, congenital amegakaryocytic

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Congenital amegakaryocytic thrombocytopenia (CAMT) presents with isolated thrombocytopenia in infancy and developing into a pancytopenia in later childhood); North West GLH: no comment submitted; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.

Created: 4 Nov 2019, 7:30 p.m. | Last Modified: 4 Nov 2019, 7:30 p.m.

Panel Version: 0.135

Comment on list classification: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.

Created: 22 Jul 2019, 1:24 p.m. | Last Modified: 22 Jul 2019, 1:24 p.m.

Panel Version: 0.79

Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: MPL; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): 10077649; 18024606

Created: 18 Feb 2019, 2:57 p.m.

Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: MPL; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): none submitted

Created: 14 Feb 2019, 5:40 p.m.

Initial gene list (Consensus Genes for Haem Panels 17.12.18_KCH.xlsx) collated by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: MPL; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 601977 Thrombocythemia 2; 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): 10077649; 11133753

Created: 8 Feb 2019, 1:43 p.m.

Green List (high evidence)

Gene rating submitted by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group.

Created: 8 Feb 2019, 1:36 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
601977 Thrombocythemia 2; 604498 Thrombocytopenia, congenital amegakaryocytic

Variants in this GENE are reported as part of current diagnostic practice