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Intellectual disability - microarray and sequencing v3.1510 ABAT Arina Puzriakova Tag for-review was removed from gene: ABAT.
Intellectual disability - microarray and sequencing v3.1510 ABAT Sarah Leigh commented on gene: ABAT: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability - microarray and sequencing v3.1509 ABAT Arina Puzriakova Source Expert Review Green was added to ABAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability - microarray and sequencing v3.1034 NEUROD2 Arina Puzriakova gene: NEUROD2 was added
gene: NEUROD2 was added to Intellectual disability. Sources: Literature
Q2_21_rating tags were added to gene: NEUROD2.
Mode of inheritance for gene: NEUROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEUROD2 were set to 16504944; 30323019; 33438828
Phenotypes for gene: NEUROD2 were set to Developmental and epileptic encephalopathy 72, OMIM:618374
Review for gene: NEUROD2 was set to GREEN
Added comment: NEUROD2 is associated with a relevant phenotype in OMIM (MIM# 618374), but is not yet listed in Gene2Phenotype.

- PMID: 30323019 (2019) - Two unrelated children with refractory early-infantile epileptic encephalopathy. Developmental delay (DD) preceded onset of seizures in both cases, with signs of DD becoming evident at 2-4 months and seizures arising at 5 months of age. Patient 1 became seizure-free after introducing a ketogenic diet at 16 months; however, an EEG at 22 months remained abnormal and she continues to have severe GDD with no independent sitting, walking or speaking at the chronological age of 3 years and 2 months. Patient 2 became seizure-free when a vagal nerve stimulator (VNS) was placed at 16 months of age. He displayed significant improvement on EEG and subsequently began regaining neurodevelopmental milestones.
WES revealed different de novo variants in the NEUROD2 gene (P1: c.388G>C, p.E130Q; P2: c.401T>C, p.M134T, respectively). Knockdown of the neurod2 in Xenopus tropicalis tadpoles resulted in abnormal swimming behaviour and progressive seizures followed by periods of immobility. Overexpression of wild-type human NEUROD2 in tadpoles induced non-neuronal cells to differentiate into neurons - on the other hand, overexpression of the mutant alleles failed to to cause any (p.E130Q) or a comparable degree (p.M134T) of ectopic neuronal induction as seen with the wild-type protein.

- Conference poster (Genomics of Rare Disease 2021) - 'Neuronal Differentiation Factor 2 (NEUROD2) Pathogenic Variant as a Molecular Aetiology of Infantile Spasm ' by Sakpichaisakul et al, QSNICH, Thailand -
In a 15 month-old female with infantile spasm, trio exome sequencing revealed a de novo variant in NEUROD2 (c.388G>C, p.E130Q). She was born of non-consanguineous healthy parents with no family history of epilepsy. Poor eye contact and no social smile were noted in the first few months, followed by the first infantile spasm at 5 months of age. This was initially controlled by combined vigabatrin and prednisolone therapy - however relapsing seizures were detected at 15 months. Sequential treatment with vigabatrin following prednisolone resulted in cessation of seizures, and subsequently regaining of neurodevelopmental milestones (sitting without support, grabbing objects without pincer grasp and speaking one single word)

----- Cases without seizures -

- PMID: 33438828 (2021) - Adolescent (14 yrs old) with GDD but without seizures who was found to have a novel de novo NEUROD2 missense variant (c.488 T > C, p.L163P). An additional individual (12 yrs) with DD and a different missense NEUROD2 (c.703G>A, p.A235T) was also identified, but lacking parental samples for segregation analysis.
Functional analysis in Xenopus laevis revealed that injection of the p.L163P mRNA variant resulted in a defective ability to induce ectopic neurons in tadpoles as compared with wild-type NEUROD2 mRNA, while the p.A235T variant functioned similarly to wild-type.
Sources: Literature
Intellectual disability - microarray and sequencing v3.342 ABAT Arina Puzriakova Classified gene: ABAT as Amber List (moderate evidence)
Intellectual disability - microarray and sequencing v3.342 ABAT Arina Puzriakova Added comment: Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team), it has been agreed that this gene should be upgraded from Amber to Green at the next major review.
Intellectual disability - microarray and sequencing v3.342 ABAT Arina Puzriakova Gene: abat has been classified as Amber List (Moderate Evidence).
Intellectual disability - microarray and sequencing v3.341 ABAT Arina Puzriakova Tag for-review tag was added to gene: ABAT.
Intellectual disability - microarray and sequencing v3.341 ABAT Arina Puzriakova reviewed gene: ABAT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GABA-transaminase deficiency, 613163; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability - microarray and sequencing v3.0 ABAT Zornitza Stark reviewed gene: ABAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 10407778, 20052547, 27596361, 28411234,; Phenotypes: GABA-transaminase deficiency, MIM#613163; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability - microarray and sequencing v2.688 ABAT Louise Daugherty Phenotypes for gene: ABAT were changed from GABA-transaminase deficiency, 613163 to GABA-transaminase deficiency, 613163; developmental delay
Intellectual disability - microarray and sequencing v2.687 ABAT Louise Daugherty Classified gene: ABAT as Amber List (moderate evidence)
Intellectual disability - microarray and sequencing v2.687 ABAT Louise Daugherty Added comment: Comment on list classification: Rated gene as Amber based on current information in the literature and external expert review there is not enough evidence to support gene-disease association rating of this gene to Green.
Intellectual disability - microarray and sequencing v2.687 ABAT Louise Daugherty Gene: abat has been classified as Amber List (Moderate Evidence).
Intellectual disability - microarray and sequencing v2.686 ABAT Louise Daugherty Publications for gene: ABAT were set to 27596361; 28411234
Intellectual disability - microarray and sequencing v2.685 ABAT Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Intellectual disability - microarray and sequencing v2.685 ABAT Louise Daugherty Publications for gene: ABAT were set to 27596361
Intellectual disability - microarray and sequencing v2.588 ABAT Konstantinos Varvagiannis reviewed gene: ABAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 28411234; Phenotypes: GABA-transaminase deficiency (MIM 613163); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability - microarray and sequencing v2.588 ABAT Konstantinos Varvagiannis Deleted their review
Intellectual disability - microarray and sequencing v2.588 ABAT Konstantinos Varvagiannis reviewed gene: ABAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 28411234; Phenotypes: GABA-transaminase deficiency (MIM 613163); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability - microarray and sequencing ABAT BRIDGE consortium edited their review of ABAT
Intellectual disability - microarray and sequencing ABAT BRIDGE consortium edited their review of ABAT
Intellectual disability - microarray and sequencing ABAT Louise Daugherty classified ABAT as amber
Intellectual disability - microarray and sequencing ABAT Louise Daugherty commented on ABAT
Intellectual disability - microarray and sequencing ABAT BRIDGE consortium reviewed ABAT