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| Skeletal ciliopathies v1.11 | EVC | Ivone Leong Added comment: Comment on phenotypes: It is also associated with ?Weyers acrofacial dysostosis, OMIM:193530. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v1.11 | EVC | Ivone Leong Phenotypes for gene: EVC were changed from Ellis-van Creveld syndrome, 225500; Weyers acrodental dysostosis, 193530 to Ellis-van Creveld syndrome, OMIM:225500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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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| Skeletal ciliopathies v0.1 | EVC2 |
Eleanor Williams gene: EVC2 was added gene: EVC2 was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: EVC2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EVC2 were set to Ellis-van Creveld syndrome, 225500; Weyers acrofacial dysostosis, 193530 |
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| Skeletal ciliopathies v0.1 | EVC |
Eleanor Williams gene: EVC was added gene: EVC was added to Skeletal ciliopathies. Sources: Emory Genetics Laboratory,Expert list,UKGTN,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: EVC was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EVC were set to Ellis-van Creveld syndrome, 225500; Weyers acrodental dysostosis, 193530 |
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