| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Limb disorders v4.4 | PRKACB | Arina Puzriakova Phenotypes for gene: PRKACB were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, OMIM:619143 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v2.69 | PRKACB | Eleanor Williams Tag for-review was removed from gene: PRKACB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v2.67 | PRKACB | Eleanor Williams commented on gene: PRKACB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v2.66 | PRKACB |
Eleanor Williams Source Expert Review Green was added to PRKACB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Limb disorders v2.18 | PRKACB | Arina Puzriakova Classified gene: PRKACB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v2.18 | PRKACB | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag) - 4 unrelated cases, all presenting polydactyly of the hands and/or feet as well as other postaxial anomalies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v2.18 | PRKACB | Arina Puzriakova Gene: prkacb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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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