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| Intellectual disability v3.1519 | NEUROD2 | Ivone Leong Tag Q2_21_rating was removed from gene: NEUROD2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.1519 | NEUROD2 | Sarah Leigh commented on gene: NEUROD2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.1519 | NEUROD2 |
Ivone Leong Source Expert Review Green was added to NEUROD2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability v3.1035 | NEUROD2 | Arina Puzriakova Classified gene: NEUROD2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.1035 | NEUROD2 | Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene as Green at the next GMS panel update - sufficient number of unrelated cases (4, plus 1 unpublished), all presenting GDD as an early feature. Particularly pertinent to less severely affected individuals who do not develop seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.1035 | NEUROD2 | Arina Puzriakova Gene: neurod2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability 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.488âTâ>âC, 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 |
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