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| Deafness_Isolated v1.40 | USP48 | Zornitza Stark Phenotypes for gene: USP48 were changed from Nonsyndromic genetic deafness, MONDO:0019497 to Deafness, autosomal dominant 85, MIM# 620227 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v1.39 | USP48 | Zornitza Stark edited their review of gene: USP48: Changed phenotypes: Deafness, autosomal dominant 85, MIM# 620227 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v1.15 | USP48 | Zornitza Stark Marked gene: USP48 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v1.15 | USP48 | Zornitza Stark Gene: usp48 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v1.15 | USP48 | Zornitza Stark Classified gene: USP48 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v1.15 | USP48 | Zornitza Stark Gene: usp48 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v1.14 | USP48 |
Zornitza Stark gene: USP48 was added gene: USP48 was added to Deafness_Isolated. Sources: Literature Mode of inheritance for gene: USP48 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: USP48 were set to 34059922 Phenotypes for gene: USP48 were set to Nonsyndromic genetic deafness, MONDO:0019497 Review for gene: USP48 was set to GREEN Added comment: PMID: 34059922 - Bassani et al 2021 - 3 cases reported with variants in USP48 and non syndromic hearing loss. They first analysed 4-generation Italian family with 6 individuals with hearing loss. The only rare variant segregating with the disease was a missense variant in USP48 (NM_032234.7:c.1216G > A, NP_115612.4:p.(Gly406Arg)). The variant is present in GnomAD v2.1.1 with a minor allele frequency (MAF) of 6.7 × 10−5 (17 allele out of 251 304 with no homozygotes). They also observed one hearing individual in the family who was heterozygous for the variant, suggesting incomplete penetrance. In a Dutch family the found by exome sequencing a missense variant in USP48 (NM_032236.7:c.2215_2216delinsTT, NP_115612.4:p.(Thr739Leu)). The probands mother and uncle were also affected by no sequence data was available for analysis. In a French family a proband is reported with right profound sensorineural hearing impairment (at 12 months), but normal left hearing (at 6 years old). The patient is heterozygote for a de novo splice variant in USP48 (NM_032236.7:c.3058 + 2 T > C, NP_115612.4:p.?;) which is not found in GnomAD and is predicted to result in a frameshift resulting in either NMD or a truncated protein. In functional experiments they showed that the two missense variants found in the Italian and Dutch families, and a shortened protein as predicted for the variant found in the French variant, showed an impaired ability to cleave tetra-ubiquitin into tri-, di- and mono-ubiquitin. Using immunohistology, they show that the human USP48 protein is present in fetal inner ear specimens. In addition zebrafish lacking usp48 showed a significant decrease of auditory response in acoustic startle response assays at 600 and 800 Hz wavelengths. Overall, borderline Green: one of the variants is present at a high frequency in the normal population. However, even if just two families are considered, supportive functional data including zebrafish model. Sources: Literature |
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