Genes in panel
STRs in panel
Prev Next

Genetic epilepsy syndromes

Gene: KATNB1

Amber List (moderate evidence)

KATNB1 (katanin regulatory subunit B1)
EnsemblGeneIds (GRCh38): ENSG00000140854
EnsemblGeneIds (GRCh37): ENSG00000140854
OMIM: 602703, Gene2Phenotype
KATNB1 is in 3 panels

3 reviews

Helen Lord (Oxford Medical Genetics Laboratories)

Red List (low evidence)

Assoc with AR lissencephaly 6 with microcephaly. Severe microcephaly and developmental delay and brain imaging shows variable malformations of cortical development including lissencephaly, pachygyria and hypoplasia of the corpus callosum. Epilepsy is reported in some patients.
Created: 23 Sep 2019, 1:08 p.m. | Last Modified: 23 Sep 2019, 1:08 p.m.
Panel Version: 1.336

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Amber, and added watchlist tag: KATNB1 was added to the panel and rated Green by Konstantinos Varvagiannis. Not yet associated with a disorder in Gene2Phenotype. Linked to lissencephaly with microcephaly in OMIM. There are sufficient cases from from the literature to support inclusion on the epilepsy panel (PMIDs:25521378, 25521379, 26640080) but epilepsy is not a feature in all cases and a Red recent review was left by Helen Lord. Therefore rated Amber as other panels may be more appropriate.
Created: 26 Sep 2019, 4:05 p.m. | Last Modified: 26 Sep 2019, 4:05 p.m.
Panel Version: 1.340
KATNB1 was added to the panel and rated Green by Konstantinos Varvagiannis. Summary of evidence is as follows (see Konstantinos Varvagiannis' review for details): 3 publications reporting patients with biallelic KATNB1 variants. The phenotype includes seizures in some, but not all cases:

PMID:25521378. Mishra-Gorur et al. 2014 report 5 families with malformations of cortical development and homozygous KATNB1 variants. In many families homozygous variants in additional genes were also reported. Epilepsy was reported in 3/7 individuals (from 2 families): Supplementary Table S1).

PMID:25521379. Hu et al., 2014 report 3 Middle Eastern families with microcephaly, Global DD and seizures, and 3 different homozygous variants in KATNB1.

PMID:26640080. Yigit el al. 2016 report a homozygous acceptor splice-site intronic KATNB1 variant in a 5 year old Turkish girl born to consanguineous cousins, who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, dental abnormalities and developmental delay. She developed seizures age 6 months.
Created: 19 Sep 2019, 12:09 p.m. | Last Modified: 26 Sep 2019, 3:53 p.m.
Panel Version: 1.336

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic pathogenic KATNB1 variants cause Lissencephaly 6, with microcephaly (MIM 616212). At least 13 affected individuals from 9 (mostly consanguineous) families have probably been reported in the following articles:

- Mishra-Gorur et al. (2014 - PMID: 25521378) [7 individuals from 5 unrelated families]
- Hu et al. (2014 - PMID: 25521379) [5 individuals from 3 families]
- Yigit el al. (2016 - PMID: 26640080) [1 subject born to consanguineous parents]

Seizures can be part of the phenotype (although not universal / reported in all 3 studies in several families). Several different variants have been reported to date. Extensive studies as for the impact of mutations at the cellular level as well as animal models (zebrafish, mouse, drosophila) support involvement of KATNB1. These arguments, provided mainly by the first two studies, are summarized in the respective OMIM entry for the disorder : https://omim.org/entry/616212 (variants and their effect are discussed in the entry for KATNB1 - https://omim.org/entry/602703).

The individual reported by Yigit el al. was a 5 year-old girl with - among others - severely delayed psychomotor development and seizures. The child was found to harbor a homozygous splice site variant (removing the acceptor AG signature). Confirmation of the variant and segregation studies were performed with Sanger sequencing. cDNA studies were carried out and demonstrated aberrant splicing.

KATNB1 is not associated with any disorder in G2P.
The gene is included in panels for ID offered by several diagnostic laboratories (incl. Radboudumc).

As a result, this gene can be considered for inclusion in the current panel probably as green (or amber).
Sources: Literature
Created: 31 Aug 2019, 10:58 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lissencephaly 6, with microcephaly (MIM 616212)

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Lissencephaly 6, with microcephaly, 616212
  • seizures
Tags
watchlist
OMIM
602703
Clinvar variants
Variants in KATNB1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

26 Sep 2019, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: KATNB1.

26 Sep 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: katnb1 has been classified as Amber List (Moderate Evidence).

19 Sep 2019, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, 616212 to Lissencephaly 6, with microcephaly, 616212; seizures

19 Sep 2019, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly (MIM 616212) to Lissencephaly 6, with microcephaly, 616212

31 Aug 2019, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Konstantinos Varvagiannis (Other)

gene: KATNB1 was added gene: KATNB1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KATNB1 were set to 25521378; 25521379; 26640080 Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly (MIM 616212) Review for gene: KATNB1 was set to GREEN