Severe microcephaly

Gene: WDR4

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

Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.

Panel Version: 2.292

Green List (high evidence)

This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There are >3 unrelated cases and therefore, there is enough evidence to support a gene-disease association. This gene should be promoted to Green at the next review.

Created: 5 May 2021, 9:14 a.m. | Last Modified: 5 May 2021, 9:14 a.m.

Panel Version: 2.118

Green List (high evidence)

PMID 26416026: 2 individuals from apparently unrelated consanguineous Egyptian families with a form of primordial dwarfism had the same homozygous missense variant. One had head circumference −10.7 SD at 20mo, the other −8.9 SD at 17mo. PMID 28617965: 2 sibs from unrelated French parents were chet for a missense variant and a frameshift variant, and had a form of primordial dwarfism. They had head circumferences of less than −5SD at ~18yo and ~16yo. Other individuals with microcephaly have been reported but without specific measurements.

Created: 31 Aug 2020, 11:16 a.m. | Last Modified: 31 Aug 2020, 11:16 a.m.

Panel Version: 2.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Galloway-Mowat syndrome 6 MIM#618347

Publications

• 26416026
• 28617965
• 30079490
• 29597095

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

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber

Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.

Panel Version: 1.62

Comment on publications: added PMID:29597095

Created: 16 Jul 2018, 8:58 a.m.

Comment on list classification: After internal clinical review it was decided to change rating from Red to Amber, based upon the two reported cases.

Created: 16 Jul 2018, 8:56 a.m.

Not associated with a disease in OMIM or Gene2Phenotype.

Created: 4 Apr 2018, 3:35 p.m.

Comment on publications: PMID: 29597095 - new publication reported biallelic variants in a 6-year old boy with Primordial dwarfism who had short statue, motor and speech delay and intellectual disability - the diagnosis of this patient in clinical was global developmental delay. Two novel variants in this gene were identified (a missense and a frameshift), one inherited from each parent.

Created: 4 Apr 2018, 3:21 p.m.

Shaheen et al., 2015 (PMID:26416026) study 2 presumably unrelated consanguineous families with an apparently novel form of microcephalic primordial dwarfism. The 2 patients were both homozygous for c.509G>T; p.Arg170Leu. Note that although the 2 families have different surnames, they come from the same geographic location in Egypt and share a single homozygous haplotype.

Created: 28 Feb 2017, 11:24 a.m.

WDR4 is on the Expert list for MPD (microcephalic primordial dwarfism) from Andrew Jackson, but with the caution that only a single mutation or family is reported in the literature.

Created: 13 Dec 2016, 12:10 p.m.