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| Intellectual disability - microarray and sequencing v2.733 | NTRK2 | Ivone Leong Classified gene: NTRK2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.733 | NTRK2 | Ivone Leong Added comment: Comment on list classification: NTRK2 has been given a green gene rating based on the expert review provided by Konstantinos Varvagiannis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.733 | NTRK2 | Ivone Leong Gene: ntrk2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.732 | NTRK2 | Ivone Leong Phenotypes for gene: NTRK2 were changed from Epileptic encephalopathy, early infantile, 58 (MIM 617830); Obesity, hyperphagia, and developmental delay (MIM 613886) to Epileptic encephalopathy, early infantile, 58, 617830; Obesity, hyperphagia, and developmental delay, 613886 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.588 | RAB11A |
Konstantinos Varvagiannis gene: RAB11A was added gene: RAB11A was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RAB11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RAB11A were set to 29100083 Phenotypes for gene: RAB11A were set to Global developmental delay; Intellectual disability Penetrance for gene: RAB11A were set to unknown Review for gene: RAB11A was set to AMBER gene: RAB11A was marked as current diagnostic Added comment: PMID: 29100083 (by Hamdan et al.) is a study on de novo mutations in individuals with developmental and epileptic encephalopathies (DEE). One subject from this study was found to harbor a de novo missense RAB11A variant [NM_004663.4:c.244C>T or p.(Arg82Cys)]. This individual presented with epilepsy, developmental regression and severe ID. In their cohort the authors also identified an additional individual with a de novo missense variant [(c.71A>G or p.(Lys24Arg)] who had moderate ID and abnormal EEG albeit without seizures. De novo variants in RAB11A had previously been identified in 3 DDD study participants with ID. The authors obtained clinical details on the 2 individuals with the p.(Ser154Leu) variant [NM_004663.4:c.461C>T]. One of them had moderate ID without seizures while the other had moderate global DD at the age of 4 years, also without seizures. A third DDD study participant harbored another missense variant p.(Lys13Asn) [NM_004663.4:c.39A>C] as a de novo occurence. The authors did not manage to obtain clinical details although this patient was reported to have abnormalities of the nervous system in Decipher. The features of all 4 individuals for whom clinical details were available are summarized in table 7. Previous studies suggest that RAB11A has a role in NTRK2 and AMPA receptor recycling at the post-synaptic membrane of neurons and - as a result - in regulation of synaptic plasticity. ----------- RAB11A is not associated with any phenotype in OMIM. This gene is included in the DD panel of G2P, associated with epilepsy and intellectual disability (disease confidence: probable). It is also included in gene panels for ID offered by some diagnostic laboratories. ----------- As a result, it can be considered for inclusion in this panel as amber or possibly green (3 unrelated individuals with ID, 1 further with DD at a young age). Sources: Literature |
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| Intellectual disability - microarray and sequencing v2.579 | NTRK2 |
Konstantinos Varvagiannis gene: NTRK2 was added gene: NTRK2 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: NTRK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NTRK2 were set to 29100083; 28135719; 15494731; 27884935 Phenotypes for gene: NTRK2 were set to Epileptic encephalopathy, early infantile, 58 (MIM 617830); Obesity, hyperphagia, and developmental delay (MIM 613886) Penetrance for gene: NTRK2 were set to unknown Review for gene: NTRK2 was set to GREEN gene: NTRK2 was marked as current diagnostic Added comment: Heterozygous pathogenic variants in NTRK2 cause Epileptic encephalopathy, early infantile, 58 (EIEE58 - MIM 617830) or Obesity, hyperphagia, and developmental delay (MIM 613886). DD/ID are among the observed features. Seizures can be noted in individuals falling into either diagnosis [eg. observed in the individuals with obesity and hyperphagia as in PMIDs: 15494731 and 29100083 (individual with Thr720Ile who presented also with moderate to severe ID)]. Concerning EIEE58 Tyr434Cys appears to be a recurrent variant that has been observed in 4 unrelated individuals (summary in table 2 from PMID: 29100083). A de novo missense variant (Gly344Cys) was observed in DDD study participant DDD4K.02136 (PMID: 28135719). NTRK2 is a probable DD gene in G2P associated with epilepsy and ID. The gene is included in gene panels for ID offered by different diagnostic laboratories (incl. Radboudumc). As a result, this gene can be considered for inclusion in this panel as green (rather than amber). Sources: Literature, Radboud University Medical Center, Nijmegen |
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