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| Intellectual disability syndromic and non-syndromic v2.108 | LDB1 | chirag patel Marked gene: LDB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.108 | LDB1 | chirag patel Gene: ldb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.108 | LDB1 | chirag patel Classified gene: LDB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.108 | LDB1 | chirag patel Gene: ldb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.107 | LDB1 |
chirag patel gene: LDB1 was added gene: LDB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: LDB1 were set to Neurodevelopmental disorder, MONDO:0700092, LDB1-related Review for gene: LDB1 was set to AMBER Added comment: ESHG 2026 16 unrelated individuals with 16 different rare heterozygous de novo variants (missense, nonsense, frameshift, gene deletions) in the LDB1 gene. Eleven variants affect the whole gene or the N-terminal dimerization domain and 5 variants affect only the C-terminus. All individuals presented with developmental delay and behaviour issues, but individuals with C-terminal variants also presented with ventriculomegaly. LDB1 encodes transcriptional regulator protein LIM-domain-binding protein 1, which plays an important role in neurogenesis. In vitro assays showed the N-terminal missense variants disrupted homodimerization of LDB1 (likely leading to a loss of function) but the C-terminal variants impaired interaction with the essential partner LHX2 (in a dominant-negative fashion). Toxicity of overexpressed human LDB1 in Drosophila was not seen for N-terminal missense variants but was exacerbated by C-terminal variants. Phenotypes associated with LDB1/chi loss in Drosophila were a) rescued by overexpression of wild-type LDB1, b) not rescued by N-terminal missense variants, and c) worsened by C-terminal variants. This suggests 2 distinct pathomechanisms of LDB1-related NDDs. Sources: Other |
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