Severe microcephaly
Gene: WDR4
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
Variants in this GENE are reported as part of current diagnostic practice
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 AmberCreated: 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:29597095Created: 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.
Source NHS GMS was added to WDR4.
Publications for gene: WDR4 were set to 26416026; 29597095
Gene: wdr4 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for WDR4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Publications for WDR4 were set to 26416026
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
Publications for WDR4 were set to 26416026
WDR4 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Expert list
WDR4 was created by rfoulger