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| Skeletal ciliopathies v3.11 | PRKACB | Eleanor Williams Tag Q2_23_promote_green was removed from gene: PRKACB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v3.11 | PRKACB | Eleanor Williams reviewed gene: PRKACB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v3.10 | PRKACB |
Eleanor Williams Source Expert Review Green was added to PRKACB. Source NHS GMS was added to PRKACB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Skeletal ciliopathies v3.5 | PRKACB | Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: PRKACB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v3.5 | PRKACB | Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber based on the evidence provided in one publication (PMID:33058759) reporting 2/4 unrelated individuals with ID among other features, although this presentation was mild in one of these cases.; to: Comment on list classification: New gene added by Konstantinos Varvagiannis. There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least 4 unrelated cases, displaying a ciliopathy-like phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v3.5 | PRKACB | Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v3.5 | PRKACB |
Arina Puzriakova gene: PRKACB was added gene: PRKACB was added to Skeletal ciliopathies. Sources: Expert Review Amber,Literature Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRKACB were set to 33058759 Phenotypes for gene: PRKACB were set to Cardioacrofacial dysplasia 2, OMIM:619143 Penetrance for gene: PRKACB were set to unknown Mode of pathogenicity for gene: PRKACB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments |
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| Skeletal ciliopathies v1.3 | PRKACA |
Zornitza Stark gene: PRKACA was added gene: PRKACA was added to Skeletal ciliopathies. Sources: Literature Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRKACA were set to 33058759; 31130284 Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth Review for gene: PRKACA was set to GREEN Added comment: This gene is difficult to place but this seems like the most appropriate panel. Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants. The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD. Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. The phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes. PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polydactyly, AVSD). By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlies the developmental defects observed in affected individuals. The authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284). Sources: Literature |
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