Haematological malignancies cancer susceptibility

Gene: IKZF1

Green List (high evidence)

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 adults

Created: 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

• 26981933
• 28096536
• 29889099
• 29681510

Green List (high evidence)

Sources: Literature

Created: 29 Jan 2021, 10:50 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
B-ALL; immunodeficiency, autoimmunity

Publications

• PMID: 29681510
• PMID: 29889099
• PMID: 27939403