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| Deafness_IsolatedAndComplex v1.57 | CDK5RAP2 |
Zornitza Stark gene: CDK5RAP2 was added gene: CDK5RAP2 was added to Deafness_IsolatedAndComplex. Sources: Expert Review Mode of inheritance for gene: CDK5RAP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CDK5RAP2 were set to 15793586; 22887808; 23995685; 23726037; 27761245; 20460369; 32677750; 32015000 Phenotypes for gene: CDK5RAP2 were set to Microcephaly 3, primary, autosomal recessive, MIM# 604804; MONDO:0011488 Review for gene: CDK5RAP2 was set to GREEN Added comment: More than 10 unrelated families and an animal model support gene-disease association. In addition to microcephaly and ID, a recent series of 7 deeply phenotyped individuals also reported small cochlea with incomplete partition type II was found in all cases, which was associated with progressive deafness in 4. Microphthalmia was also present in all along with retinal pigmentation changes and lipofuscin deposits. Finally, hypothalamic anomalies consisting of interhypothalamic adhesions, a congenital midline defect usually associated with holoprosencephaly, was detected in 5 cases. Sources: Expert Review |
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| Deafness_IsolatedAndComplex v0.533 | WHRN |
Zornitza Stark changed review comment from: Association with Usher syndrome: DEFINITIVE by ClinGen, multiple families and animal models. Of note, the Whrn(neo/neo) mouse model, in which the N-terminal and long transcripts are ablated, leads to Usher syndrome (Mather et al. 2015, PMID: 26307081). Associated with isolated AR deafness: MODERATE by ClinGen. Of note, the Whrn(wi/wi) model, which disrupts only the long and C-terminal transcripts, results in a mouse with profound hearing loss and severe vestibular defect without a retinal phenotype (Ebrahim et al. 2016, PMID: 27117407). The Whrn(tm1b/tm1b) model disrupts the C-terminal transcripts, resulting in a mouse with mild-hearing loss and no vestibular or retinal defects (Ebrahim et al. 2016, PMID: 27117407). Several families reported with AR deafness, however, in many reports, there is insufficient phenotyping to be certain an eye phenotype is absent.; to: Multiple transcripts with differential tissue expression exist for WHRN which are thought to explain the basis for distinct phenotypes. The long transcript is expressed in the retina, vestibule and cochlea, whereas the C-terminal transcript is expressed exclusively in the cochlea and vestibule and the N-terminal transcript is expressed exclusively in the retina (Ebrahim et al. 2016, PMID: 27117407). Association with Usher syndrome: DEFINITIVE by ClinGen, multiple families and animal models. Of note, the Whrn(neo/neo) mouse model, in which the N-terminal and long transcripts are ablated, leads to Usher syndrome (Mather et al. 2015, PMID: 26307081). Associated with isolated AR deafness: MODERATE by ClinGen. Of note, the Whrn(wi/wi) model, which disrupts only the long and C-terminal transcripts, results in a mouse with profound hearing loss and severe vestibular defect without a retinal phenotype (Ebrahim et al. 2016, PMID: 27117407). The Whrn(tm1b/tm1b) model disrupts the C-terminal transcripts, resulting in a mouse with mild-hearing loss and no vestibular or retinal defects (Ebrahim et al. 2016, PMID: 27117407). Several families reported with AR deafness, however, in many reports, there is insufficient phenotyping to be certain an eye phenotype is absent. |
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| Deafness_IsolatedAndComplex v0.473 | COCH | Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094Deafness, autosomal recessive 110, MIM# 618094 to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.472 | COCH | Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, autosomal dominant 9, MIM# 601369 to Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094Deafness, autosomal recessive 110, MIM# 618094 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.471 | COCH | Zornitza Stark Publications for gene: COCH were set to 16151338; 28116169; 28099493; 9806553; 17561763; 21046548; 26256111; 22931125; 22610276; 18312449; 28733840; 18697796; 29449721 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.470 | COCH |
Zornitza Stark changed review comment from: Over 50 affected individuals from more than 10 families reported, mouse model. Single family with two siblings reported with bi-allelic variants in this gene and deafness (homozygous LOF) in PMID 29449721, evidence for bi-allelic disease is limited.; to: Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated. Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050. |
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| Deafness_IsolatedAndComplex v0.470 | COCH | Zornitza Stark edited their review of gene: COCH: Changed publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721, 32939038, 32562050 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.470 | COCH | Zornitza Stark edited their review of gene: COCH: Changed phenotypes: Deafness, autosomal dominant 9, MIM# 601369, Deafness, autosomal recessive 110, MIM# 618094 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.433 | COCH | Zornitza Stark Marked gene: COCH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.433 | COCH | Zornitza Stark Gene: coch has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.433 | COCH | Zornitza Stark edited their review of gene: COCH: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.433 | COCH | Zornitza Stark Mode of inheritance for gene: COCH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.432 | COCH | Zornitza Stark Phenotypes for gene: COCH were changed from to Deafness, autosomal dominant 9, MIM# 601369 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.431 | COCH | Zornitza Stark Publications for gene: COCH were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.430 | COCH | Zornitza Stark Mode of inheritance for gene: COCH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.429 | COCH | Zornitza Stark reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721; Phenotypes: Deafness, autosomal dominant 9, MIM# 601369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deafness_IsolatedAndComplex v0.353 | CNRIP1 |
Zornitza Stark gene: CNRIP1 was added gene: CNRIP1 was added to Deafness. Sources: Literature Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CNRIP1 were set to 32337552; 19159392 Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654 Review for gene: CNRIP1 was set to RED Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members. Sources: Literature |
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| 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 |
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| Deafness_IsolatedAndComplex v0.342 | FOXF2 |
Zornitza Stark gene: FOXF2 was added gene: FOXF2 was added to Deafness. Sources: Literature Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FOXF2 were set to 30561639; 22022403 Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea Review for gene: FOXF2 was set to AMBER Added comment: Single family: variant has functional data to demonstrate effect on protein, plus mouse model supports gene-disease association. Sources: Literature |
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| Deafness_IsolatedAndComplex v0.328 | PLOD3 |
Lauren Akesson gene: PLOD3 was added gene: PLOD3 was added to Deafness. Sources: Literature Mode of inheritance for gene: PLOD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLOD3 were set to 18834968; 31129566 Phenotypes for gene: PLOD3 were set to Sensorineural deafness Penetrance for gene: PLOD3 were set to unknown Review for gene: PLOD3 was set to GREEN Added comment: This gene has a complex phenotype that includes features of a connective tissue disorder; 3/5 described unrelated families have sensorineural deafness as a feature (PMID as above plus an abstract from 2013 ESHG by Steichen-Gersdorf et al). At least one proband has required cochlear implantation. Sources: Literature |
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| Deafness_IsolatedAndComplex v0.0 | COCH |
Zornitza Stark gene: COCH was added gene: COCH was added to Deafness_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Deafness Flagship Mode of inheritance for gene: COCH was set to Unknown |
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