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| Skeletal dysplasia v5.3 | ERI1 | Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v5.3 | ERI1 |
Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ERI1. Tag Q4_23_NHS_review was removed from gene: ERI1. |
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| Skeletal dysplasia v5.3 | ERI1 | Achchuthan Shanmugasundram commented on gene: ERI1: The rating of this gene has been updated togreenand the mode of inheritance updated to 'BIALLELIC, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v5.2 | ERI1 |
Achchuthan Shanmugasundram Source Expert Review Green was added to ERI1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Skeletal dysplasia v4.25 | ERI1 | Achchuthan Shanmugasundram Classified gene: ERI1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.25 | ERI1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promotion of this gene to green rating in the next GMS review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.25 | ERI1 | Achchuthan Shanmugasundram Gene: eri1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.24 | ERI1 | Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: ERI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.24 | ERI1 |
Achchuthan Shanmugasundram changed review comment from: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia.; to: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia (PMID:37352860). This gene has not yet been associated with relevantly phenotypes either in OMIM or in Gene2Phenotype. |
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| Skeletal dysplasia v4.24 | ERI1 | Achchuthan Shanmugasundram commented on gene: ERI1: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.24 | ERI1 | Achchuthan Shanmugasundram Phenotypes for gene: ERI1 were changed from spondyloepimetaphyseal dysplasia; digital anomalies to spondyloepimetaphyseal dysplasia, MONDO:0100510 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.23 | ERI1 | Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ERI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.23 | ERI1 | Achchuthan Shanmugasundram reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37352860; Phenotypes: spondyloepimetaphyseal dysplasia, MONDO:0100510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.18 | ERI1 | Tracy Lester edited their review of gene: ERI1: Added comment: >3 cases confirmed; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.18 | ERI1 |
Tracy Lester gene: ERI1 was added gene: ERI1 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERI1 were set to 37352860 Phenotypes for gene: ERI1 were set to spondyloepimetaphyseal dysplasia; digital anomalies Penetrance for gene: ERI1 were set to unknown Mode of pathogenicity for gene: ERI1 was set to Other Added comment: In this study, the authors uncovered a phenotypic dichotomy in eight individuals from seven unrelated families with different types of ERI1 variants and highlighted the association of missense variants with spondyloepimetaphyseal dysplasia (SEMD), which is a group of skeletal diseases characterized by anomalies in spine and long tubular bones.In contrast, the affected individuals with bi-allelic null variants showed mild intellectual disability and digital anomalies. The detailed evaluation of the skeletal phenotypes of Eri1 knockout (KO) mice and the in vitro chondrogenesis of affected-individual-derived induced pluripotent stem cells (iPSCs) supported the functional involvement of ERI1 in skeletal development. Analyses using ERI1 KO HeLa cells and affected-individual-derived cells demonstrated functional conservation of ERI1 with its mouse ortholog in 5.8S rRNA maturation and histone mRNAs decay. The 5.8S rRNA maturation is involved in ribosome biogenesis, defects of which are known to cause ribosomopathies characterized by skeletal dysplasia.12–15 Our study leads to the findings of an SEMD associated with ribosomopathy and established a framework for understanding the molecular mechanisms underlying the ERI1 phenotypic dichotomy. Missense variants reported to affect residues 134,150, 155, 298 and 299. All cases with biallelic missense variants had short stature, epiphyseal, spinal and digit anomalies, as well as other variable kidney and cardiac anomalies. One case with a LOF and a missense was reported with these features and intellectual disability/developmental delay. The 3 cases with biallelic LOF variants had ID/DD, digital anomalies without the other (height varied from 8th centile to normal). Sources: NHS GMS |
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