Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
10 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.20 | LDB1 | Achchuthan Shanmugasundram Phenotypes for gene: LDB1 were changed from Congenital hydrocephalus, MONDO:0016349 to neurodevelopmental disorder, MONDO:0700092; congenital hydrocephalus, MONDO:0016349 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.19 | LDB1 | Achchuthan Shanmugasundram Publications for gene: LDB1 were set to 39680505; 38091987; 33077954 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.18 | LDB1 | Achchuthan Shanmugasundram Mode of pathogenicity for gene: LDB1 was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.17 | LDB1 |
Achchuthan Shanmugasundram changed review comment from: PMID:42320471 (2026) reported a cohort of 16 individuals with de novo LDB1 variants, of which 14 patients presented with developmental delay, 13 patients with speech delay and 8 patients with motor delay. There were eight other patients reported previously. Developmental delay was present in 9/11 individuals with N-terminal LGD/DD missense variants and 7/7 individuals with C-terminal LID-affecting variants, speech delay present in 10/10 and 5/5, and motor delay present in 5/9 and 5/5 respectively. Unlike the ventriculomegaly phenotype, developmental delay occurs across both N-terminal and C-terminal variant classes, indicating it is a core, mechanism-independent feature of LDB1-related neurodevelopmental disorder. N-terminal DD missense variants impair LDB1 homodimerization through loss-of-function, while C-terminal LID variants abolish LHX2 binding via a dominant-negative mechanism, both disrupting transcriptional complexes required for neurogenesis. In Drosophila, neuronal knockdown of the LDB1 ortholog chi impaired motor behavior, and both variant types failed to properly rescue this phenotype, confirming LDB1 dysfunction causally contributes to neurological/developmental impairment. This gene has not yet been associated with relevant phenotypes in OMIM, Gene2Phenotype or ClinGen.; to: PMID:42320471 (2026) reported a cohort of 16 individuals with de novo LDB1 variants, of which 14 patients presented with developmental delay, 13 patients with speech delay and 8 patients with motor delay. There were eight other patients reported previously. Developmental delay was present in 9/11 individuals with N-terminal LGD/DD missense variants and 7/7 individuals with C-terminal LID-affecting variants, speech delay present in 10/10 and 5/5, and motor delay present in 5/9 and 5/5 respectively. Unlike the ventriculomegaly phenotype, developmental delay occurs across both N-terminal and C-terminal variant classes, indicating it is a core, mechanism-independent feature of LDB1-related neurodevelopmental disorder. N-terminal DD missense variants impair LDB1 homodimerization through loss-of-function, while C-terminal LID variants abolish LHX2 binding via a dominant-negative mechanism, both disrupting transcriptional complexes required for neurogenesis. In Drosophila, neuronal knockdown of the LDB1 ortholog chi impaired motor behavior, and both variant types failed to properly rescue this phenotype, confirming LDB1 dysfunction causally contributes to neurological/developmental impairment. This gene has not yet been associated with relevant phenotypes in OMIM, Gene2Phenotype or ClinGen (last accessed 16 August 2026). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.17 | LDB1 | Achchuthan Shanmugasundram reviewed gene: LDB1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 42320471; Phenotypes: neurodevelopmental disorder, MONDO:0700092, congenital hydrocephalus, MONDO:0016349; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.206 | LDB1 | Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: LDB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.194 | LDB1 | Arina Puzriakova Classified gene: LDB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.194 | LDB1 |
Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Although ventriculomegaly and/or hydrocephalus are the primary feature of the disorder, at least seven unrelated individuals have been reported with GDD and several also exhibited hypotonia. Taking this into account and the broader syndromic presentation, it would be appropriate to include this gene on the R27 Paediatric disorders and R69 Hypotonic infant super panels, both of which incorporate Intellectual disability as a component panel. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.194 | LDB1 | Arina Puzriakova Gene: ldb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.193 | LDB1 |
Arina Puzriakova gene: LDB1 was added gene: LDB1 was added to Intellectual disability. Sources: Literature Q4_25_promote_green tags were added to gene: LDB1. Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LDB1 were set to 39680505; 38091987; 33077954 Phenotypes for gene: LDB1 were set to Congenital hydrocephalus, MONDO:0016349 Review for gene: LDB1 was set to GREEN Added comment: - Allington et al. 2024 (PMID: 39680505) investigate a cohort of 2697 trios with congenital primary cerebral ventriculomegaly using WES. Eight unrelated individuals identified with de novo variants in LDB1 (7 LOF, 1 predicted damaging missense) - exhibiting perinatally diagnosed cerebral ventriculomegaly, including neurosurgically treated congenital hydrocephalus. Additionally, 5/8 GDD, 3/8 autism, 2/8 delayed gross motor development, 2/8 had congenital heart defects (inc. coarctation, PDA), 2/8 camptodactyly. Additional case was identified from GeneMatcher with a de novo frameshift variants in LDB1. Phenotypes include severe ventriculomegaly, absence of well formed gyri, severe limb contractures and camptodactyly. Search of Decipher/DDD also revealed 4 pathogenic de novo variants in LDB1 and associated binding partners in individuals congenital ventriculomegaly. - Torene et al. 2023 (PMID: 38091987) identified three individuals with protein truncating variants. Two individuals with de novo variants both had ventriculomegaly, hypotonia, GDD, craniofacial abnormalities. The third individual inherited the variants from an asymptomatic mother, and displayed developmental delay, hypotonia, congenital heart defects and a small hypoplastic hippocampi but did not have ventriculomegaly or craniofacial anomalies. - Jin et al. 2020 (PMID: 33077954) also report an individual with a de novo LOF variant in this gene who had congenital hydrocephalus but details on this case are otherwise limited. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||