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| Intellectual disability - microarray and sequencing v3.1513 | MAPK1 | Arina Puzriakova Tag for-review was removed from gene: MAPK1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1510 | MAPK1 | Sarah Leigh commented on gene: MAPK1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1509 | MAPK1 |
Arina Puzriakova Source Expert Review Green was added to MAPK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v3.939 | MAPK10 | Catherine Snow Source: Expert Review Red was removed from gene: MAPK10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.554 | MAPK1 | Catherine Snow Tag for-review tag was added to gene: MAPK1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.554 | MAPK1 | Catherine Snow Classified gene: MAPK1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.554 | MAPK1 | Catherine Snow Gene: mapk1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.553 | MAPK1 | Catherine Snow reviewed gene: MAPK1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32721402; Phenotypes: Noonan syndrome 13, OMIM:619087, MONDO:0018997; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.253 | MAPK10 | Arina Puzriakova commented on gene: MAPK10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.219 | MAPK1 |
Konstantinos Varvagiannis gene: MAPK1 was added gene: MAPK1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MAPK1 were set to 32721402 Phenotypes for gene: MAPK1 were set to Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin Penetrance for gene: MAPK1 were set to unknown Mode of pathogenicity for gene: MAPK1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: MAPK1 was set to GREEN Added comment: Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants. The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once. MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway. MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic). The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome). The authors comment that screening of 267 additional individuals with suspected RASopathy (without mutations in previously implicated genes) did not reveal other MAPK1 variants. Overall this gene can be considered for inclusion in the ID panel with green rating. Sources: Literature |
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| Intellectual disability - microarray and sequencing v3.3 | MAPK10 | Zornitza Stark reviewed gene: MAPK10: Rating: RED; Mode of pathogenicity: None; Publications: 23329067, 16249883; Phenotypes: Intellectual disability, seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.510 | TRAF7 |
Konstantinos Varvagiannis gene: TRAF7 was added gene: TRAF7 was added to Intellectual disability. Sources: Expert Review,Literature Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRAF7 were set to 29961569; 27479843; 28135719; 25363760; 25961944 Phenotypes for gene: TRAF7 were set to Global developmental delay; Abnormal heart morphology; Abnormality of digit; Abnormality of limbs Penetrance for gene: TRAF7 were set to unknown Review for gene: TRAF7 was set to GREEN Added comment: PMID: 29961569 reports on 7 unrelated individuals with pathogenic variants in TRAF7. Common features included developmental delay, congenital heart defects, limb and digital anomalies as well as shared facial features (including epicanthal folds, ptosis, abnormal ears, excess nuchal skin). Two (or possibly three) of these patients had seizures. Some of these individuals had been investigated in the past for disorders of the Ras-MAPK pathway (CFC, Noonan and Costello syndrome). The SNVs reported are missense and occured de novo in all patients for whom parental studies were possible (6 out of 7). A recurrent mutation [p.(Arg655Gln)] was found in 4 of the 7 individuals. One patient was found to harbor a mutation in the mosaic state, as a de novo occurrence. The variants resulted in reduced activation of ERK1/2 (also known as MAPK3/MAPK1). // 7 individuals with de novo coding variants have previously been reported in large cohorts of patients with intellectual disability (PMIDs : 27479843, 28135719 - DDD study) and/or ASD (25363760, 25961944). One of the individuals from the DDD study had a stopgain variant. The individuals from these studies are summarized in the denovo-db (http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=TRAF7). // As a result this gene can be considered for inclusion in the ID panel as green (or amber). Sources: Expert Review, Literature |
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