Haematological malignancies cancer susceptibility
Gene: IKZF1
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 10:30 a.m. | Last Modified: 3 Mar 2022, 10:30 a.m.
Panel Version: 2.23
Comment on list classification: New gene added by Kiran Tawana (Addenbrooke's Hospital, Cambridge). Several studies indicate that coding germline IKZF1 variants are a risk factor for genetic predisposition to ALL. Therefore, this gene may be promoted to Green at the next panel update following GMS review (added 'for-review' tag)Created: 2 Feb 2021, 4:30 p.m. | Last Modified: 2 Feb 2021, 4:30 p.m.
Panel Version: 2.10
Germline IKZF1 variation has been reported in cases of both familial and sporadic Acute lymphoblastic leukaemia (ALL):
- Kuehn et al. 2016 (PMID: 26981933) reported on a cohort 29 individuals from six families with germline IKZF1 variants and immunodeficiency, of which 2 patients developed B-cell ALL at ages 3 and 5, respectively.
- Yoshida et al. 2017 (PMID: 28096536) describe a female with severe IKZF1-related immunodeficiency that later progressed to T-cell ALL at 13 years of age. This same individual was also reported on as patient F1 by Boutboul et al. 2018 (PMID: 29889099)
- Churchman et al. 2018 (PMID: 29681510) identified 28 unique germline IKZF1 coding variants in 45 children with ALL. Functional studies revealed that majority of these variants had deleterious effects on IKAROS function.
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Somatic variants also have a well-recognised role in the development of ALL in both children and adultsCreated: 2 Feb 2021, 4:27 p.m. | Last Modified: 2 Feb 2021, 4:27 p.m.
Panel Version: 2.9
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Acute lymphoblastic leukemia (ALL); Immunodeficiency, common variable, 13, OMIM:616873
Publications
Tag for-review was removed from gene: IKZF1.
Source Expert Review Green was added to IKZF1. Source NHS GMS was added to IKZF1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: IKZF1 were set to PMID: 29681510; PMID: 29889099; PMID: 27939403
Gene: ikzf1 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: IKZF1.
Phenotypes for gene: IKZF1 were changed from B-ALL; immunodeficiency, autoimmunity to Acute lymphoblastic leukaemia (ALL); Immunodeficiency, common variable, 13, OMIM:616873
gene: IKZF1 was added gene: IKZF1 was added to Haematological malignancies cancer susceptibility. Sources: Literature Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IKZF1 were set to PMID: 29681510; PMID: 29889099; PMID: 27939403 Phenotypes for gene: IKZF1 were set to B-ALL; immunodeficiency, autoimmunity Penetrance for gene: IKZF1 were set to unknown Review for gene: IKZF1 was set to GREEN