| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Deafness_IsolatedAndComplex v1.260 | REST | Chirag Patel Marked gene: REST as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v1.260 | REST | Chirag Patel Gene: rest has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v1.247 | Chirag Patel Copied gene REST from panel Deafness_Isolated | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v1.247 | REST |
Chirag Patel gene: REST was added gene: REST was added to Deafness_IsolatedAndComplex. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: REST were set to 29961578; 34828371 Phenotypes for gene: REST were set to Deafness, autosomal dominant 27, MIM# 612431 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v1.225 | TBX2 |
Zornitza Stark gene: TBX2 was added gene: TBX2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Mode of inheritance for gene: TBX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TBX2 were set to 20206336; 22052739; 21271665; https://doi.org/10.1101/2024.07.18.24310488 Phenotypes for gene: TBX2 were set to Hearing loss disorder, MONDO:0005365, TBX2-related Review for gene: TBX2 was set to AMBER Added comment: There is some emerging evidence for the association of TBX2 and monogenic hearing loss. Several reported individuals with de novo microdeletions encompassing TBX2 had sensorineural hearing loss as one of the symptoms (PMID: 20206336 Ballif et al., 2010; PMID: 22052739 Schönewolf-Greulich et al., 2011; PMID: 21271665 Nimmakayalu et al., 2011). TBX2 and TBX4 are suggested as strong candidate genes. However, the effect of other genes being deleted is hard to decouple. A study by Hua et al. ( https://doi.org/10.1101/2024.07.18.24310488, pre-print, posted in July 2024) identified two Chinese families with late onset progressive sensorineural hearing loss. Affected members in each family were heterozygous for c.977delA p.(Asp326Alafs*42) and c.987delC p.(Ala330Argfs*38) respectively. Both variants are extremely rare and co-segregate with disease. Method: Linkage analysis + WGS. Family 1: five generations, 21/102 individuals had hearing loss (AD inheritance). Age of onset 4-40 years old. Monitoring at 10 year intervals showed slowly progressive auditory decline. 9 family member also exhibited spontaneous nystagmus (onset 0-5 years). Caveat: Six other shared variants were identified in RKD3, DYNC2LI1, FAHD2A, OR5K3, TBX2, ZNF135 - autosomal dominant pattern. Family 2: 4/14 members had hearing loss, proband had severe hearing loss with onset before 5yo; patient II.6 had late onset hearing loss (onset at 26-30yo) with nystagmus observed in childhood. Functional data: Tbx2 is essential for inner hair cell (IHC) differentiation in mice. Conditional Tbx2 knockout causes embryonic IHCs differentiate as outer hair cells (OHCs). Both inner and outer hair cells are required for hearing (PMID: 35508658 Garcia-Anoveros et al., 2022). Tbx2-/- knockout mouse embryos exhibit lethal cardiovascular defects (PMID: 15459098 Harrelson et a., 2004). In https://doi.org/10.1101/2024.07.18.24310488, Tbx2-/- mice were also embryonic lethal. Heterozygous Tbx2+/- mice had normal Auditory Brainstem Response thresholds at day 70. They started showing signs of hearing loss at day 100, and they exhibited severe hearing loss at day 150 – consistent with late-onset hearing loss reported in some patients. Interestingly, p.(Asp326Alafs*42) knock-in mice did not show any signs of hearing loss. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.344 | TBL1Y |
Zornitza Stark gene: TBL1Y was added gene: TBL1Y was added to Deafness. Sources: Literature Mode of inheritance for gene: TBL1Y was set to Other Publications for gene: TBL1Y were set to 30341416 Phenotypes for gene: TBL1Y were set to Hearing loss Review for gene: TBL1Y was set to RED Added comment: Y-linked inheritance pattern. Complete segregation of a missense variant demonstrated in 9 affected males in a 5-generation pedigree. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||