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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
Intellectual disability v8.55 EEFSEC Achchuthan Shanmugasundram Phenotypes for gene: EEFSEC were changed from neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.54 EEFSEC Achchuthan Shanmugasundram gene: EEFSEC was added
gene: EEFSEC was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: EEFSEC was set to GREEN
Added comment: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v3.421 UROS Arina Puzriakova Source Expert Review Red was added to UROS.
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Intellectual disability v3.254 UROS Arina Puzriakova commented on gene: UROS
Intellectual disability v3.3 RPGRIP1 Zornitza Stark reviewed gene: RPGRIP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 13, MIM# 608194, Leber congenital amaurosis 6, MIM# 613826; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 RPE65 Zornitza Stark reviewed gene: RPE65: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 2, MIM# 204100, Retinitis pigmentosa 20, MIM# 613794, Retinitis pigmentosa 87 with choroidal involvement, MIM# 618697; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.3 NMNAT1 Zornitza Stark reviewed gene: NMNAT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 9, MIM# 608553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.3 UROS Zornitza Stark reviewed gene: UROS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Porphyria, congenital erythropoietic, MIM# 263700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability UROS BRIDGE consortium edited their review of UROS
Intellectual disability UROS Louise Daugherty classified UROS as amber
Intellectual disability UROS Louise Daugherty commented on UROS
Intellectual disability UROS BRIDGE consortium reviewed UROS