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| Intellectual disability v3.1564 | PPP1R21 | Eleanor Williams Tag gene-checked tag was added to gene: PPP1R21. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.1166 | PPP1R21 |
Ivone Leong Added comment: Comment on phenotypes: Previously: Hepatosplenomegaly;Abnormality of the respiratory system;Generalized hypotonia, Feeding difficulties, Profound global developmental delay, Abnormality of the face, Abnormality of vision, Abnormal heart morphology |
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| Intellectual disability v3.1166 | PPP1R21 | Ivone Leong Phenotypes for gene: PPP1R21 were changed from Hepatosplenomegaly; Abnormality of the respiratory system; Generalized hypotonia, Feeding difficulties, Profound global developmental delay, Abnormality of the face, Abnormality of vision, Abnormal heart morphology to Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, OMIM:619383 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.989 | PPP1R21 | Catherine Snow Phenotypes for gene: PPP1R21 were changed from Hepatosplenomegaly; Abnormality of the respiratory system; Generalized hypotonia, Feeding difficulties, Profound global developmental delay, Abnormality of the face, Abnormality of vision, Abnormal heart morphology, Abnormality of the respiratory system to Hepatosplenomegaly; Abnormality of the respiratory system; Generalized hypotonia, Feeding difficulties, Profound global developmental delay, Abnormality of the face, Abnormality of vision, Abnormal heart morphology | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.988 | PPP1R21 | Catherine Snow Phenotypes for gene: PPP1R21 were changed from Hepatosplenomegaly; Abnormality of the respiratory system; Generalized hypotonia, Feeding difficulties, Profound global developmental delay, Abnormality of the face, Abnormality of vision, Abnormal heart morphology, Abnormality of the respiratory system, Hepatosplenomegaly; Profound global developmental delay; Abnormal heart morphology; Generalized hypotonia; Feeding difficulties; Abnormality of the face; Abnormality of vision to Hepatosplenomegaly; Abnormality of the respiratory system; Generalized hypotonia, Feeding difficulties, Profound global developmental delay, Abnormality of the face, Abnormality of vision, Abnormal heart morphology, Abnormality of the respiratory system | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.978 | PPP1R21 |
Catherine Snow Source Expert Review Green was added to PPP1R21. Source Expert Review was added to PPP1R21. Added phenotypes Generalized hypotonia, Feeding difficulties, Profound global developmental delay, Abnormality of the face, Abnormality of vision, Abnormal heart morphology, Abnormality of the respiratory system, Hepatosplenomegaly for gene: PPP1R21 Rating Changed from No List (delete) to Green List (high evidence) |
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| Intellectual disability v2.596 | PPP1R21 | Louise Daugherty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.596 | PPP1R21 | Louise Daugherty commented on gene: PPP1R21: this is a test comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.596 | PPP1R21 | Louise Daugherty Added comment: Comment on publications: added publications recommended by external reviews | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.596 | PPP1R21 | Louise Daugherty Publications for gene: PPP1R21 were set to 29808498; 28940097 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.579 | PPP1R21 | Zornitza Stark reviewed gene: PPP1R21: Rating: GREEN; Mode of pathogenicity: None; Publications: 30520571, 29808498, 2894097; Phenotypes: severe intellectual disability, hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.576 | PPP1R21 |
Konstantinos Varvagiannis gene: PPP1R21 was added gene: PPP1R21 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PPP1R21 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP1R21 were set to 29808498; 28940097 Phenotypes for gene: PPP1R21 were set to Generalized hypotonia; Feeding difficulties; Profound global developmental delay; Abnormality of the face; Abnormality of vision; Abnormal heart morphology; Abnormality of the respiratory system; Hepatosplenomegaly Penetrance for gene: PPP1R21 were set to Complete Review for gene: PPP1R21 was set to GREEN Added comment: Biallelic pathogenic variants in PPP1R21 have been reported so far in 9 individuals from 7 unrelated families. All (7 different) variants reported to date are truncating. PMID: 29808498 is the first detailed clinical description on the related phenotype. 3 individuals from 3 families are reported. One of these individuals was previously included in a larger patient cohort (in PMID: 28940097). In a subsequent further publication, Rehman et al. (https://doi.org/10.1002/humu.23694) describe 6 additional patients from 4 unrelated consanguineous families. Again, these individuals were homozygous for truncating mutations. The authors summarize the findings in their patients as well as the previously reported ones. Common features included feeding difficulties, hypotonia with severe global DD and mildly coarsened facial features (all were observed in 9/9), visual anomalies (8/9), respiratory problems (7/9), cardiac anomalies (4/9) and hepato-/splenomegaly (3/7). Brain MRI anomalies were observed in the majority. DD was severe in all and ID (which is not explicitly mentioned) was evident from the clinical description of several individuals (eg. in PMID: 29808498). In total 7 loss-of-function variants have been reported. The authors in the first article, underscore the possibility of less severe phenotypes associated to biallelic missense variants (although none has been reported so far). Functional studies have shown great reduction (but not complete absence) of PPP1R21 mRNA levels in patient fibroblasts compared to controls. A role of PPP1R21 in the endosomal-lysosomal function is demonstrated in line with the presence of myelin figures in patient fibroblasts as well as some phenotypic similarities to neurometabolic/lysosomal storage disorders. Most variants reported in the most recent publication except one (NM_001135629.2:c.1607dupT) seem to affect all 3 PPP1R21 isoforms (which also seems to be the case for previously published variants). c.1607dupT appears to be the single truncating variant affecting 2 (of 3) isoforms. This variant was however shown to have severely reduced expression in fibroblasts upon qPCR, absent protein staining, and increase in myelin figures. The protein is expressed in embryonic mouse cortex. Overall, this gene can be considered for inclusion in this panel as green (or amber). Sources: Literature |
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