Deafness_IsolatedAndComplex
Gene: TUBB4B
ESHG 2023:
De novo heterozygous TUBB4B variants found in:
-8 patients with recurrent respiratory infections (PCD phenotype), irregular corpus callosum, and dilated ventricles (suggesting motile cilia anomaly)
-3 patients with retinal dystrophy, SNHL, and PCD respiratory issues
Functional studies:
-variants showed decreased cilia number and length, and mislocalisation of dyenin motors
-mouse models had decreased cilia number and length in trachea, and reduction in cilia in choroid plexus cells leading to hydrocephalyCreated: 25 Jul 2023, 2:22 a.m. | Last Modified: 25 Jul 2023, 2:22 a.m.
Panel Version: 1.157
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Primary ciliary dyskinesia
Phenotypes
Leber congenital amaurosis with early-onset deafness, MIM# 617879
The TUBB4B gene has been associated with autosomal dominant Leber congenital amaurosis with early-onset deafness using the ClinGen Clinical Validity Framework as of 6/12/2018. This association was made using case-level data only. At least 2 missense variants have been reported de novo in humans, p.Arg391His and p.Arg391Cys. TUBB4B was first associated with this disease in humans in 2017 (Luscan et al.). Association is seen in at least 4 probands in 1 publication (29198720). Variants in this gene segregated with disease in 3 additional family members. This gene-disease association is supported by an in vitro functional assay. According to Luscan et al. 2017, the Arg391, Arg390 and Lys392 residues form a binding pocket that interacts with alpha-tubulin in the longitudinally adjacent tubulin alpha-beta-heterodimer. It is possible that a substitution at Arg391 destabilizes the hydrophobic interactions between the residues.Created: 28 Jan 2020, 11:36 p.m. | Last Modified: 28 Jan 2020, 11:36 p.m.
Panel Version: 0.265
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Leber congenital amaurosis with early-onset deafness
Publications
Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness to Leber congenital amaurosis with early-onset deafness, MIM# 617879
Gene: tubb4b has been classified as Green List (High Evidence).
Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness to Leber congenital amaurosis with early-onset deafness
Phenotypes for gene: TUBB4B were changed from Leber congenital amaurosis with early-onset deafness to Leber congenital amaurosis with early-onset deafness
Phenotypes for gene: TUBB4B were changed from to Leber congenital amaurosis with early-onset deafness
Publications for gene: TUBB4B were set to 29198720
Publications for gene: TUBB4B were set to
Mode of inheritance for gene: TUBB4B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
gene: TUBB4B was added gene: TUBB4B was added to Deafness_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Deafness Flagship Mode of inheritance for gene: TUBB4B was set to Unknown