Severe microcephalyGene: ZNF335
Comment on mode of inheritance: Changed MOI from 'biallelic' to 'both monoallelic and biallelic' based on information from Chicago University about ClinVar variant c.2515_2518dupGCCA (p.Thr840Serfs).
1 Mar 2017, 10:09 a.m.
Comment on list classification: Updated rating from Red to Amber: 1 published case plus 1 case in-press plus mouse model. Changed rating to Amber until the Baylor lab paper at least is published, and more information is available about additional variants.
1 Mar 2017, 10:03 a.m.
1 further 'likely pathogenic' variant submitted to ClinVar by Chicago lab, under 'Primary autosomal recessive microcephaly 10':
The lab confirmed that they saw this variant in one patient, who was reported to have microcephaly, encephalopathy and developmental delay. The variant was heterozygous, and no second variant was found by either sequencing or deletion/duplication studies.
1 Mar 2017, 10:01 a.m.
2 further 'Pathogenic' variants submitted to ClinVar by Baylor, under 'Primary autosomal recessive microcephaly 10':
Correspondance with the Baylor lab revealed that the proband's phenotype was developmental delay, intellectual disability, seizures, hypomyelination, failure to thrive. A paper is currently in press in Genome Medicine.
1 Mar 2017, 10:01 a.m.
1 case in literature/OMIM: PMID:23178126 (Yang et al., 2012) identify 3332G-A (ARG1111HIS) in affected members of an Arab Israeli family. PMID:26479514 (Nishida et al., 2016) discuss anaesthesia in a female patient with MCPH-10 and a ZNF335 gene mutation, but don't discuss the mutation in further detail.
28 Feb 2017, 11:48 a.m.
Mutations only identified in one family but supported by mouse model
12 Jan 2017, 11:16 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
?Microcephaly 10, primary, autosomal recessive 615095
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.
Mode of inheritance for ZNF335 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
This gene has been classified as Amber List (Moderate Evidence).
Publications for ZNF335 were set to 25951892; 25548773; 23178126
ZNF335 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Source: Other Model of inheritance for gene ZNF335 was set to BIALLELIC, autosomal or pseudoautosomal
ZNF335 was created by rfoulger
ZNF335 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Literature