Hearing lossGene: TOP2B
Comment on list classification: Changing the rating from grey to amber. 1 familial case plus 3 sporadic cases reported. Supportive animal model. All reported in one publication so will wait until there is an additional supporting familial case before rating green.
Created: 8 Sep 2020, 9:09 p.m. | Last Modified: 8 Sep 2020, 9:09 p.m.
Panel Version: 2.56
Not associated with a phenotype in OMIM.
PMID: 31198993 - Xia et al 2019 - Whole-exome sequencing was performed on seven affected and six unaffected members in a large Chinese family with autosomal-dominant nonsyndromic hearing loss. A variant in TOP2B (c.G4837C:p.D1613H) segregated with hearing loss in this family. Two other variants of TOP2B were detected in 66 sporadic patients with hearing loss (p.L721F and p. K1435del, plus another case with p.D1613H). In zebrafish, top2b knockdown led to defects in the inner ears and caused downregulation of akt which resulted in inactivation of PI3K-Akt signalling.
Created: 8 Sep 2020, 9:02 p.m. | Last Modified: 8 Sep 2020, 9:08 p.m.
Panel Version: 2.55
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
nonsyndromic hearing loss
One multigenerational family where variant in this gene segregated with deafness; two additional variants identified in a cohort; supportive animal model data.
Sources: Expert list
Created: 2 Jan 2020, 5:50 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Deafness, autosomal dominant
Phenotypes for gene: TOP2B were changed from Deafness, autosomal dominant to Deafness, autosomal dominant; nonsyndromic hearing loss
Gene: top2b has been classified as Amber List (Moderate Evidence).
gene: TOP2B was added gene: TOP2B was added to Hearing loss. Sources: Expert list Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: TOP2B were set to 31198993 Phenotypes for gene: TOP2B were set to Deafness, autosomal dominant