Intellectual disability - microarray and sequencing
Gene: ACBD6
Limited G2P gene. Evidence curated for analysis of a heterozygous exon 7 deletion detected by SNP array.
PMID: 37951597: Emerging evidence that biallelic variants in ACBD6 cause a neurodevelopmental syndrome. Three individuals from families 23 and 24 with homozygous exon 7 deletion, Moderate GDD/ID.
Three individuals from families 12 and 13 with splice variants resulting in skipping of exon 7, GDD/ID.Created: 20 Feb 2024, 12:30 p.m. | Last Modified: 20 Feb 2024, 12:30 p.m.
Panel Version: 5.451
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
HP:0001263; HP:0001249
Publications
Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)Created: 23 Apr 2024, 1:38 p.m. | Last Modified: 23 Apr 2024, 1:38 p.m.
Panel Version: 5.536
Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.Created: 17 Jan 2024, 5:22 p.m. | Last Modified: 17 Jan 2024, 5:22 p.m.
Panel Version: 5.405
- PMID: 21937992 (2011) - single individuals with a p.G22fs variant in the ACBD6 gene, presenting with mild ID, microcephaly, facial dysmorphism, spasticity. Limited additional information.
- PMID: 32108178 (2020) - two unrelated individuals with neurodevelopmental disorder (moderate ID is noted but otherwise limited clinical information) and carrying homozygous LoF variants in the ACBD6 gene (1 frameshift, 1 canonical splice). One individual also carried an allelic homozygous variant in the PRDX6 gene (unlikely but unknown disease consequence). Skin-derived patient fibroblasts showed reduced ACBD6 expression and N-myristoylation deficiency.
- PMID: 36457943 (2023) - two Thai siblings presenting with profound ID, morbid obesity, pancytopenia with severe recurrent infections, diabetes mellitus, cirrhosis, and renal failure, leading to deaths in their early 30s. Sequencing showed a novel homozygous single bp duplication (c.360dup; p.Leu121Thrfs*27) in the ACBD6 gene. Parents were heterozygous carriers.
- PMID: 37951597 (2023) - 45 previously undiagnosed individuals from 28 families with a neurodevelopmental syndrome including a complex and progressive movement disorder phenotype. Cardinal clinical features include moderate-to-severe GDD/ID (45/45), facial dysmorphism (38/40), HC <2nd percentile (21/31), weight >50th percentile (20/34), mild cerebellar ataxia (35/41), limb spasticity/hypertonia (31/41), gait abnormalities (33/35), dystonia (30/32) and variable epilepsy (13/29).
Homozygous ACBD6 variants were identified by WES in all cases, including 18 predicted LoF, 1 missense and 1 inframe insertion. Knockout studies in zebrafish recapitulate clinical features reported in patients such as movement disorders, seizures, and facial dysmorphology, while inactivation of acbd6 in X. tropicalis predominantly caused embryo death while surviving tadpoles demonstrated microcephaly, reduced movement, eye abnormalities, and brain structure differences.Created: 17 Jan 2024, 5:12 p.m. | Last Modified: 17 Jan 2024, 5:12 p.m.
Panel Version: 5.402
Comment on publications: PMID: 32108178 (2020) paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniquesCreated: 17 Jan 2024, 3:58 p.m. | Last Modified: 17 Jan 2024, 3:58 p.m.
Panel Version: 5.402
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder, MONDO:0700092
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
AUTOSOMAL RECESSIVE MENTAL RETARDATION
Publications
ACBD6 variants have not been associated with a phenotype in OMIM, and as an autosomal recessive condition with Limited strength in Gen2Phen. Three variants have been reported in three unrelated cases with intellectual disability, however, in one of these carriers the ACBD6 variant was allelic with PRDX6 gene c.136del; p.(ValCysfs*23), therefore the contribution of the ACBD6 variant to intellectual disability is uncertain in this case (PMID: 21937992, 32108178).Created: 15 Jan 2024, 3:31 p.m. | Last Modified: 15 Jan 2024, 3:31 p.m.
Panel Version: 5.400
Single variant found as only change in one ID familyCreated: 31 Oct 2017, 9:57 a.m.
Phenotypes
Intellectual disability
Publications
Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Publications for gene: ACBD6 were set to 21937992; 32108178
Phenotypes for gene: ACBD6 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092
Tag Q1_24_promote_green tag was added to gene: ACBD6.
Publications for gene: ACBD6 were set to 21937992; 32108178
Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Publications for gene: ACBD6 were set to 21937992
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
ACBD6 was added to Intellectual disabilitypanel. Sources: Expert Review Red
ACBD6 was created by ellenmcdonagh