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| Early onset or syndromic epilepsy v2.281 | KATNB1 | Arina Puzriakova Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, 616212; seizures to Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.342 | KATNB1 | Rebecca Foulger Tag watchlist tag was added to gene: KATNB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.340 | KATNB1 | Rebecca Foulger Classified gene: KATNB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.340 | KATNB1 | Rebecca Foulger Added comment: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.340 | KATNB1 | Rebecca Foulger Gene: katnb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.336 | KATNB1 |
Rebecca Foulger changed review comment from: KATNB1 was added to the panel and rated Grey 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.; to: 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. |
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| Early onset or syndromic epilepsy v1.336 | KATNB1 | Helen Lord reviewed gene: KATNB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.333 | KATNB1 | Rebecca Foulger Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly, 616212 to Lissencephaly 6, with microcephaly, 616212; seizures | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.332 | KATNB1 | Rebecca Foulger commented on gene: KATNB1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.332 | KATNB1 | Rebecca Foulger Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly (MIM 616212) to Lissencephaly 6, with microcephaly, 616212 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.260 | KATNB1 |
Konstantinos Varvagiannis 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 Added comment: 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 |
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