Monogenic hearing loss
Gene: CRYM
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 10:16 a.m. | Last Modified: 30 Jan 2023, 10:16 a.m.
Panel Version: 3.7
In addition to the two previously described families, an additional Chinese NSHL family with a missense variant in CRYM was recently described.
The variant (Pro51Leu) has 2 hets in gnomad. The family consists of 30 individuals, 7 affected. The variant segregated with the phenotype.Created: 5 Mar 2021, 4:58 a.m. | Last Modified: 5 Mar 2021, 4:58 a.m.
Panel Version: 2.156
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Deafness, autosomal dominant 40 MIM#616357
Publications
Comment on list classification: Leaving rating as red but with green recommendation following GMS review. 3 cases now reported, 1 in a family of significant size. Expression data to show that this protein is express in the ear.Created: 9 Jun 2021, 6:35 p.m. | Last Modified: 9 Jun 2021, 6:35 p.m.
Panel Version: 2.171
Associated with Deafness, autosomal dominant 40 #616357 (AD) in OMIM.
PMID: 32742378 - Wang et al 2020 - report a 4 generation Chinese family with 31 members, of which 7 have hearing loss. WES identified a heterozygous missense mutation in CRYM (c.152C>T; Pro51Leu) which segregated with the phenotype in the family. As Zornitza Stark reports gnomad (3.1.1) has 2 hets reported (allele freq of 1.32e-5).
PMID: 12471561 - Abe et al 2003 - used genome-wide cDNA microarray analysis to investigate gene-expression profiles in human cochlea and vestibule and identified CRYM as a candidate gene. They then screened CRYM, among 192 patients with nonsyndromic deafness. Two unrelated Japanese patients were identified with variants in CRYM; one with a de novo change (c.945A→T, p.X315Y) which results in an extended protein in a patient with unaffected parents, and the other was a missense mutation (c.941A→C;p.K314T) that segregated dominantly in the proband’s family.
PMID: 16740909 - Oshima et al 2006 - looked at the effect of the two variants found by Abe et al, X315Y and K314T by looking at T3 binding activity of the mutant μ‐crystallin (product of CRYM) proteins. They found the K314T mutation impaired the NADPH dependent T3 binding (but did not find this for the X315Y variant). They also showed that μ‐crystallin protein localisation in mouse cochlea using immunocytochemical methods.
PMID: 18448257 - Usami et al 2009 - showed that Crym protein localizes in type II fibrocytes of the spiral ligament in the cochlea in mice and rats
PMID: 24676347 - Yoshimura et al 2014 - show a gradient of gene expression of CRYM in mouse cochlea
PMID: 26915689 - Hosoya et al 2016 - immunohistochemical analysis of expression of CRYM in cochlea of a non-human primate, the common marmoset and found a different expression pattern compared to mouse, with expression not only in the lateral wall spiral ligament and the spiral limbus, but also in both inner and outer hair cells, supporting cells.Created: 9 Jun 2021, 6:31 p.m. | Last Modified: 9 Jun 2021, 6:31 p.m.
Panel Version: 2.168
I think the Abe et al 2003 publication referred to by Emma Ashton is PMID: 12471561 not PMID 420014Created: 1 May 2019, 2:03 p.m.
After review with the NHS GMS hearing specialist group on 2019-02-13 it was decided to keep this gene red.Created: 18 Feb 2019, 11:24 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Deafness, autosomal dominant 40, OMIM:616357; autosomal dominant nonsyndromic deafness 40, MONDO:0014603
Publications
1 publication only 2 variants nonsyndromic deafness. Abe et al 2003 PMID 420014. No further DM report since. Nothing found by us. OMIM #616357Created: 17 Feb 2019, 4:35 p.m.
Publications
Comment on list classification: Two reviewers suggesting this should be demoted from green to red due to unconvincing evidence at this time.Created: 17 Feb 2016, 1 p.m.
very few convincing mutationsCreated: 13 Oct 2015, 8:27 p.m.
Tag Q2_21_rating was removed from gene: CRYM.
Source NHS GMS was added to CRYM. Source Expert Review Green was added to CRYM. Rating Changed from Red List (low evidence) to Green List (high evidence)
Gene: crym has been classified as Red List (Low Evidence).
Tag Q2_21_rating tag was added to gene: CRYM.
Phenotypes for gene: CRYM were changed from hearing loss; Deafness, autosomal dominant 40 to Deafness, autosomal dominant 40, OMIM:616357; autosomal dominant nonsyndromic deafness 40, MONDO:0014603
Publications for gene: CRYM were set to 12471561; 1384048; 1478656; 16740909; 9328354
Publications for gene: CRYM were set to PMID:12471561; 1384048; 1478656; 16740909; 9328354
This gene has been classified as Red List (Low Evidence).
Publications for CRYM were set to PMID:12471561; 1384048; 1478656; 16740909; 9328354
Mode of inheritance for CRYM was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Red List (Low Evidence).
CRYM was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
CRYM was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
CRYM was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
CRYM was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert