| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Skeletal dysplasia v1.115 | LRRFIP1 | chirag patel Marked gene: LRRFIP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.115 | LRRFIP1 | chirag patel Gene: lrrfip1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.115 | LRRFIP1 |
chirag patel gene: LRRFIP1 was added gene: LRRFIP1 was added to Skeletal dysplasia. Sources: Other deep intronic tags were added to gene: LRRFIP1. Mode of inheritance for gene: LRRFIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: LRRFIP1 were set to Spondylodysplastic-erosive early-onset scoliosis Review for gene: LRRFIP1 was set to RED Added comment: ESHG 2026 Multiple individuals from 1 large multigenerational family with early-onset scoliosis, with a unique pattern of spondylodysplastic elements and progressive endplate erosion. Penetrance was 100% in the family. Linkage analysis and WGS identified a rare noncoding variant in the regulatory element in intron 1 of the LRRFIP1 gene (c.96+34737C>T). The variant segregated with disease in the family. Short- and long-read RNA sequencing in patient fibroblasts showed altered transcription factor binding and alteration of relative LRRFIP1-isoform expression. Differential gene expression analyses in patient fibroblasts showed alterations in Wnt-signaling during somitogenesis, extracellular matrix organization and TNF-a/NF-kb signaling, partially overlapping with features of common spinal disorders such as Ankylosing Spondylitis. Lrrfip1-knockout mouse had a significantly increased prevalence of kyphoscoliosis. Rare variant enrichment analysis using genome data from UK Biobank participants showed significant enrichment of LRRFIP1-variants in individuals with idiopathic scoliosis. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||