Severe microcephaly
Gene: ZNF335
Comment on mode of inheritance: Other than the one case that was reported by Chicago lab with ZNF335 heterozygous variant (c.2515_2518dupGCCA/ p.Thr840Serfs) and with microcephaly, encephalopathy and developmental delay, all other cases reported in the literature and ClinVar had biallelic variants in ZNF335. Hence, the MOI should be updated to "BIALLELIC, autosomal or pseudoautosomal" in the next GMS review.Created: 21 Feb 2024, 8:40 p.m. | Last Modified: 21 Feb 2024, 8:40 p.m.
Panel Version: 4.60
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
NO evidence for being BOTH monoallelic and biallelic. Should be changed to biallelic only.Created: 25 Jan 2024, 12:06 p.m. | Last Modified: 25 Jan 2024, 12:06 p.m.
Panel Version: 4.53
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.
Panel Version: 2.282
Comment on list classification: There is enough evidence for this gene to be rated Green at the next GMS panel update (added 'for-review' tag).Created: 27 Oct 2020, 12:12 p.m. | Last Modified: 27 Oct 2020, 12:12 p.m.
Panel Version: 2.34
Associated with relevant phenotype in OMIM, but currently not in Gene2Phenotype.
At least 6 unrelated families reported in literature with different biallelic variants in ZNF335. All affected individuals present with severe congenital or acquired microcephaly (OFC < -3SD), with the exception of one less severely affected case (patient B from PMID:29652087), in whom head circumference at 3 months was −1.22 SD. Functional analyses have corroborated implication in this phenotype, including a supportive animal model.Created: 27 Oct 2020, 12:11 p.m. | Last Modified: 27 Oct 2020, 12:11 p.m.
Panel Version: 2.33
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephaly 10, primary, autosomal recessive, 615095
Publications
At least 3 unrelated individuals with severe microcephaly (-3.24SD, -5SD, -9SD). Variants are all missense or in-frame del.Created: 31 Aug 2020, 6:51 a.m. | Last Modified: 31 Aug 2020, 6:51 a.m.
Panel Version: 2.19
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephaly 10, primary, autosomal recessive (MIM#615095)
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 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).Created: 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.Created: 1 Mar 2017, 10:03 a.m.
1 further 'likely pathogenic' variant submitted to ClinVar by Chicago lab, under 'Primary autosomal recessive microcephaly 10':
NM_022095.3(ZNF335):c.2515_2518dupGCCA (p.Thr840Serfs)
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.Created: 1 Mar 2017, 10:01 a.m.
2 further 'Pathogenic' variants submitted to ClinVar by Baylor, under 'Primary autosomal recessive microcephaly 10':
NM_022095.3(ZNF335):c.3787G>T (p.Glu1263Ter)
NM_022095.3(ZNF335):c.2744_2747delGTGA (p.Ser915Thrfs)
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.Created: 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.Created: 28 Feb 2017, 11:48 a.m.
Mutations only identified in one family but supported by mouse modelCreated: 12 Jan 2017, 11:16 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Microcephaly 10, primary, autosomal recessive 615095
Publications
Tag Q1_24_MOI tag was added to gene: ZNF335. Tag Q1_24_expert_review tag was added to gene: ZNF335.
Mode of inheritance for gene: ZNF335 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ZNF335 were changed from Microcephaly 10, primary, autosomal recessive, 615095 to Microcephaly 10, primary, autosomal recessive, OMIM:615095
Tag for-review was removed from gene: ZNF335.
Source Expert Review Green was added to ZNF335. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: ZNF335 were set to 25951892; 25548773; 23178126
Phenotypes for gene: ZNF335 were changed from Autosomal recessive primary microcephaly (MCPH) ; ?Microcephaly 10, primary, autosomal recessive, 615095 to Microcephaly 10, primary, autosomal recessive, 615095
Gene: znf335 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: ZNF335.
Source NHS GMS was added to ZNF335.
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 added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Literature
ZNF335 was created by rfoulger