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| Deafness_Isolated v1.74 | CPD |
Sarah Milton changed review comment from: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to play role in the cochlea. PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands. All variants appropriately rare in gnomad v4 for a rare recessive disorder. No homozygous loss of function variants in gene in gnomad v4. Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function. Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper. Authors suggest potential treatment of affected individuals with arginine supplementation. Sources: Literature; to: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to play role in the cochlea. PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands. All variants appropriately rare in gnomad v4 for a rare recessive disorder. No homozygous loss of function variants in gene in gnomad v4. All families consanguineous Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function. Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper. Authors suggest potential treatment of affected individuals with arginine supplementation. Sources: Literature |
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| Deafness_Isolated v1.74 | CPD |
Sarah Milton gene: CPD was added gene: CPD was added to Deafness_Isolated. Sources: Literature Mode of inheritance for gene: CPD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPD were set to PMID: 41026541 Phenotypes for gene: CPD were set to Nonsyndromic genetic hearing loss, MONDO:0019497, CPD-related Review for gene: CPD was set to GREEN Added comment: CPD encodes carboxypeptidase D which is part of the metallocarboxylpeptidases family. These enzymes are zinc dependent and cleave c terminal arginine and lysine. Which in turn has a role in production of nitric oxide which is known to play role in the cochlea. PMID: 41026541 describes 5 individuals from 3 families with biallelic missense variants in CPD who have prelingual onset bilateral profound SNHL. No syndromic features were noted in affected probands. All variants appropriately rare in gnomad v4 for a rare recessive disorder. No homozygous loss of function variants in gene in gnomad v4. Functional studies demonstrated reduction in nitric oxide levels in patient cells as well as increased apoptosis with rescue upon introduction on L arginine. Proposed mechanism of disease is loss of function. Drosophila studies demonstrated disrupted Johnston’s organ morphology and impaired auditory transduction with partial rescue by arginine. Other supportive functional models discussed in paper. Authors suggest potential treatment of affected individuals with arginine supplementation. Sources: Literature |
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| Deafness_Isolated v1.8 | GREB1L |
Zornitza Stark gene: GREB1L was added gene: GREB1L was added to Deafness_Isolated. Sources: Expert list Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GREB1L were set to 29955957; 32585897 Phenotypes for gene: GREB1L were set to Deafness, autosomal dominant 80, MIM# 619274 Review for gene: GREB1L was set to GREEN Added comment: DFNA80 is characterized by nonsyndromic congenital deafness associated with absent or malformed cochleae and eighth cranial nerves. Four unrelated families reported, no comment on a renal phenotype. Note variants in this gene are also associated with renal agenesis. Sources: Expert list |
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| Deafness_Isolated v0.41 | COCH | Zornitza Stark Marked gene: COCH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v0.41 | COCH | Zornitza Stark Gene: coch has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v0.41 | COCH | Zornitza Stark Phenotypes for gene: COCH were changed from Non syndromic deafness to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v0.40 | COCH | Zornitza Stark Publications for gene: COCH were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_Isolated v0.0 | COCH |
Zornitza Stark gene: COCH was added gene: COCH was added to DeafnessIsolated. Sources: Melbourne Genomics Health Alliance Deafness Flagship,Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: COCH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: COCH were set to Non syndromic deafness |
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