Monogenic hearing loss
Gene: LMX1AThe mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' 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
The MOI of this gene should be reviewed at the next update to consider whether it should be set to Both mono and bi-allelicCreated: 3 Mar 2022, 1:44 p.m. | Last Modified: 3 Mar 2022, 1:44 p.m.
Panel Version: 2.230
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 1:19 p.m. | Last Modified: 3 Mar 2022, 1:19 p.m.
Panel Version: 2.221
Comment on list classification: Changing rating from red to amber but with a recommendation for a green rating following GMS review.Created: 25 Nov 2020, 4:54 p.m. | Last Modified: 25 Nov 2020, 4:54 p.m.
Panel Version: 2.120
Comment on mode of inheritance: Setting MOI to Monoallelic as only one case of biallelic reported to dateCreated: 25 Nov 2020, 4:52 p.m. | Last Modified: 3 Mar 2022, 1:42 p.m.
Panel Version: 2.230
Associated with Deafness, autosomal dominant 7 #601412 (AD) in OMIM.
As reported by Zornitza Stark, 3 families with monoallelic missense variants and 1 family with biallelic. Mouse model and some functional data showing decreased transcriptional activity as a result of the reported variants.
PMID: 29754270- Wesdorp et al 2018 - report 2 families of Dutch origin with progressive nonsyndromic hearing impairment. Using WES they identified heterozygous variants in LMX1A in both families. In family one, c.721G > C; p.Val241Leu was found in 3 generations. In the second family, c.290G > C;p.Cys97Ser was found in the affected mother and 3 affected children. Age of onset ranged from birth to 35 years.
PMID: 29971487 - Schrauwen et al 2018 - report a consanguineous Pakistani family with severe-to-profound hearing impairment that is inherited in an autosomal recessive manner. They identified a homozygous missense variant c.1106T>C:p.Ile-369Thr in LMX1A in 2 affected children using exome sequencing. The parents were heterozygous carriers.
PMID: 32840933 - Lee et al 2020 - report a 3 month year old proband with severe-to-profound hearing loss from birth, in which a de novo, heterozygous, missense variant (c.595A > G; p.Arg199Gly) in LMX1A was identified by exome sequencing. Functional studies to measure the transcriptional activity of the 3 heterozygous LMX1A variants showed the greatest reduction with p.Arg199Gly, followed by p.Cys97Ser and p.Val241Leu which are associated with a less severe phenotype. The activity of the p.Ile-369Thr variant (found in the biallelic case) was only slightly reduced.
Mouse models - PMID: 19540218 and PMID:18985389 both report LMX1A knockout mouse have ear defects.Created: 25 Nov 2020, 4:36 p.m. | Last Modified: 25 Nov 2020, 4:36 p.m.
Panel Version: 2.116
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Deafness, autosomal dominant 7 OMIM:601412; autosomal dominant nonsyndromic deafness 7 MONDO:0011074
Publications
Now 3 families with monoallelic missense variants (2 with dominant inheritance and 1 de novo), and a single biallelic family. Supporting mouse model and in vitro functional assays.Created: 5 Oct 2020, 9:04 a.m. | Last Modified: 5 Oct 2020, 9:04 a.m.
Panel Version: 2.94
Two families described with mono-allelic variants and dominant pattern of deafness; one family with bi-allelic. Mouse model.Created: 2 Jan 2020, 4:58 a.m. | Last Modified: 2 Jan 2020, 4:58 a.m.
Panel Version: 2.4
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Deafness, autosomal recessive and autosomal dominant
Publications
Publications for gene: LMX1A were set to 29754270; 29971487; 32840933; 19540218; 18985389
Tag Q1_22_MOI was removed from gene: LMX1A.
Source NHS GMS was added to LMX1A. Mode of inheritance for gene LMX1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag Q1_22_MOI tag was added to gene: LMX1A.
Tag watchlist was removed from gene: LMX1A. Tag for-review was removed from gene: LMX1A.
Source Expert Review Green was added to LMX1A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag watchlist tag was added to gene: LMX1A. Tag for-review tag was added to gene: LMX1A.
Gene: lmx1a has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: LMX1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: LMX1A were changed from to Deafness, autosomal dominant 7 OMIM:601412; autosomal dominant nonsyndromic deafness 7 MONDO:0011074
Publications for gene: LMX1A were set to
LMX1A was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Expert