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Severe microcephaly

Gene: ZNF335

Amber List (moderate evidence)

ZNF335 (zinc finger protein 335)
EnsemblGeneIds (GRCh38): ENSG00000198026
EnsemblGeneIds (GRCh37): ENSG00000198026
OMIM: 610827, Gene2Phenotype
ZNF335 is in 4 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

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

Zornitza Stark (Australian Genomics)

Green List (high evidence)

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

Louise Daugherty (Genomics England Curator)

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

Rebecca Foulger (Genomics England curator)

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.

Alice Gardham (Genomics England)

I don't know

Mutations only identified in one family but supported by mouse model
Created: 12 Jan 2017, 11:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Microcephaly 10, primary, autosomal recessive 615095

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
  • Literature
Phenotypes
  • Microcephaly 10, primary, autosomal recessive, 615095
Tags
for-review
OMIM
610827
Clinvar variants
Variants in ZNF335
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

27 Oct 2020, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: ZNF335 were set to 25951892; 25548773; 23178126

27 Oct 2020, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

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

27 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: znf335 has been classified as Amber List (Moderate Evidence).

27 Oct 2020, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: ZNF335.

29 Jul 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to ZNF335.

2 Mar 2017, Gel status: 2

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

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.

1 Mar 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for ZNF335 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

1 Mar 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

28 Feb 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for ZNF335 were set to 25951892; 25548773; 23178126

13 Dec 2016, Gel status: 0

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

ZNF335 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Source: Other Model of inheritance for gene ZNF335 was set to BIALLELIC, autosomal or pseudoautosomal

13 Dec 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

ZNF335 was created by rfoulger

13 Dec 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

ZNF335 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Literature