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| Mendeliome v1.3301 | 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. 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; 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 assist in function of 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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| Mendeliome v1.3300 | CPD | Zornitza Stark Marked gene: CPD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3300 | CPD | Zornitza Stark Gene: cpd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3300 | CPD | Zornitza Stark Classified gene: CPD as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3300 | CPD | Zornitza Stark Gene: cpd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3288 | 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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| Mendeliome v1.3288 | CPD |
Sarah Milton gene: CPD was added gene: CPD was added to Mendeliome. 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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| Mendeliome v0.10427 | TECRL |
Zornitza Stark gene: TECRL was added gene: TECRL was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TECRL were set to 17666061; 27861123; 30790670; 33367594 Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021 Review for gene: TECRL was set to GREEN Added comment: DEFINITIVE by ClinGen Homozygous or cpd heterozygous pathogenic variants in TECRL have been identified in patients with CPVT in at least 3 families in the literature with functional evidence. - 17666061 one consanguineous family with 4 affected relatives (siblings or 1stcousins) - 27861123 consanguineous family with 8 affected relatives (siblings or 1stcousins) - 30790670 reported in a single family with one child with features of CPVT -A multi-centre review published in 2020 provided an update on these cases and described two additional CPVT cases (homozygous p.Tyr197Ter nonsense variant and homozygous exon 2 deletion) and a family with three children with sudden cardiac death, where one was homozygous for the c.331+1G>A splice donor variant, PMID 33367594 Sources: Expert Review |
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