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Skeletal dysplasia v4.10 | EN1 |
Eleanor Williams changed review comment from: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model.; to: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model. It has been additionally added to the 'Fetal anomalies' and 'Ataxia and cerebellar anomalies - narrow panel' panels based on the phenotype. If more cases with intellectual disability/seizures are reported then it could be additionally added to those panels at that time. |
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Skeletal dysplasia v4.10 | EN1 | Eleanor Williams Tag watchlist tag was added to gene: EN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v4.10 | EN1 | Eleanor Williams commented on gene: EN1: The Genomics England clinical team confirm that the rating of this gene should currently be amber based on 1 case and a mouse model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v4.7 | EN1 | Eleanor Williams Classified gene: EN1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v4.7 | EN1 |
Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. One patient with a loss of function variant in this gene and a skeletal phenotype reported, plus mouse model with this gene knocked out also shows a skeletal phenotype. A further 3 patients with 27 and 63Kb deletions 300Kb upstream of this gene also show a skeletal phenotype and this appears to be due to ablation of a long non-coding RNA loci (in mice). However, at this distance it is unlikely to be detected by the Genomics England rare disease pipeline as being associated with EN1, and there are currently no regions on Skeletal dysplasia panel covering that area of chr 2. Therefore, at the present time this gene should be rated amber, following confirmation by the clinical team. |
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Skeletal dysplasia v4.7 | EN1 | Eleanor Williams Gene: en1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v4.6 | EN1 | Eleanor Williams commented on gene: EN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Skeletal dysplasia v2.83 | EN1 |
Zornitza Stark gene: EN1 was added gene: EN1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EN1 were set to 33568816 Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217; ENDOVE syndrome, limb-brain type, MIM# 619218 Review for gene: EN1 was set to GREEN gene: EN1 was marked as current diagnostic Added comment: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. An additional fourth individual had cerebellar hypoplasia in addition to the skeletal phenotype, and a bi-allelic LoF variant. Sources: Literature |