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| Limb disorders v4.11 | PRKACA | Eleanor Williams Tag Q2_23_promote_green was removed from gene: PRKACA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v4.11 | PRKACA | Eleanor Williams reviewed gene: PRKACA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v4.10 | PRKACA |
Eleanor Williams Source NHS GMS was added to PRKACA. Source Expert Review Green was added to PRKACA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Limb disorders v4.5 | PRKACA | Arina Puzriakova Entity copied from Skeletal ciliopathies v3.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v4.5 | PRKACA |
Arina Puzriakova gene: PRKACA was added gene: PRKACA was added to Limb disorders. Sources: Expert Review Amber,Literature Q2_23_promote_green tags were added to gene: PRKACA. 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 Cardioacrofacial dysplasia 1, OMIM:619142 |
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| Limb disorders v2.17 | PRKACB |
Arina Puzriakova gene: PRKACB was added gene: PRKACB was added to Limb disorders. Sources: Literature for-review tags were added to gene: PRKACB. 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 Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability Review for gene: PRKACB was set to GREEN Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 4 individuals heterozygous for PRKACB pathogenic variants. The most characteristic features in all individuals with PRKACB variants, included postaxial polydactyly of hands (3/4 bilateral, 1/4 unilateral) and feet (3/4 bilateral), clinodactyly (2/4), brachydactyly (1/4) and congenital heart defects (CHD 4/4) namely a common atrium or AVSD. Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumours. Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). WES was carried out in all. 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo. Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt). By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signalling likely underlies the developmental defects observed in affected individuals. Sources: Literature |
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