Monogenic short stature

Gene: ZFP57

Comment on phenotypes: Previous phenotypes include: IUGR;Multi Locus Imprinting Disturbance

Created: 26 Mar 2024, 4:18 p.m. | Last Modified: 26 Mar 2024, 4:18 p.m.

Panel Version: 3.62

Green List (high evidence)

Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 7 unrelated cases of diabetes mellitus, transient neonatal 1 OMIM:601410, who shared pattern of mosaic hypomethylation and a conserved range of clinical features (PMID 18622393). Therefore, variants in ZFP57 can be regarded as responsible for this Multi Locus Imprinting Disturbance.

Created: 2 Feb 2021, 4:42 p.m. | Last Modified: 2 Feb 2021, 4:42 p.m.

Panel Version: 1.55

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 1:49 p.m. | Last Modified: 3 Mar 2022, 1:49 p.m.

Panel Version: 1.100

Comment on list classification: Promoted from Red to Amber. The GMS specialist group needs to determine whether this phenotype is appropriate for the panel. If appropriate then can be promoted to Green.

Created: 1 Feb 2021, 2:27 p.m. | Last Modified: 1 Feb 2021, 2:27 p.m.

Panel Version: 1.48

ZFP57 causes multi-locus imprinting disturbance and as yet this always includes transient neonatal diabetes and IUGR; but sometimes diabetes is missed and so a baby could have unexplained IUGR and therefore fit into this panel.

Created: 29 Jan 2021, 11:39 a.m. | Last Modified: 29 Jan 2021, 11:39 a.m.

Panel Version: 1.34

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
IUGR; transient neonatal diabetes

Publications

• Mackay DJG, JLA Calloway, SM Marks, HE White, CL Acerini, SE Boonan, P Dayanikli, HV Firth, JA Goodship, AP Haemers, JMD Hahnemann, O Kordonouri, AF Masoud, E Ostergaard, J Storr, S Ellard, AT Hattersley, DO Robinson, IK Temple. Hypomethylation at multiple imprinted loci in individuals with transient neonatal diabetes is associated with ZFP57 mutations Nature Genetics: 2008
• 40: 949-51. PMID: 18622393. DOI: 10.1038/ng.187

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

I don't know

Following discussion with members of the Endocrine Specialist Group at the Webex call on 23.05.19, it was agreed that this gene was outside the scope of this clinical indication. Therefore demoted gene from Green to Red.

Created: 30 May 2019, 9:49 a.m.