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Hearing loss

Gene: DMXL2

Amber List (moderate evidence)

DMXL2 (Dmx like 2)
EnsemblGeneIds (GRCh38): ENSG00000104093
EnsemblGeneIds (GRCh37): ENSG00000104093
OMIM: 612186, Gene2Phenotype
DMXL2 is in 12 panels

4 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 29 Jun 2020, 3:25 p.m. | Last Modified: 29 Jun 2020, 3:25 p.m.
Panel Version: 2.27
Comment on mode of inheritance: updating to both monoallelic and biallelic, as deafness with both type of inheritance are reported, although more with biallelic
Created: 29 Jun 2020, 3:14 p.m. | Last Modified: 29 Jun 2020, 3:14 p.m.
Panel Version: 2.24
After consultation with Genomics England clinical team it has been decided to rate this gene green as, although hearing loss presents with epileptic encephalopathy, hearing loss is a consistent and early feature.
Created: 29 Jun 2020, 3:11 p.m. | Last Modified: 29 Jun 2020, 3:11 p.m.
Panel Version: 2.23
Provisionally associated with ?Deafness, autosomal dominant 71 #617605 (AD) in OMIM

Only one family reported to date with autosomal dominant deafness (PubMed: 27657680 Chen et al 2017).

As Zornitza Stark notes there are 3 new cases reported with bialllelic variants presenting with hearing loss along with other phenotypic features - PMID: 31688942 -Esposito et al 2019 - identified biallelic DMXL2 mutations in three sibling pairs with Ohtahara syndrome, belonging to three unrelated families. The severe developmental and epileptic encephalopathy manifested from the first day of life and was associated with deafness, mild peripheral polyneuropathy and dysmorphic features.

Consulting with Genomics England clinical team as to whether this gene is suitable for inclusion with a biallelic mode of inheritance on this panel.
Created: 28 Jan 2020, 10:47 a.m. | Last Modified: 28 Jan 2020, 10:47 a.m.
Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Deafness, autosomal dominant 71, 617605

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Additional recent publication of bi-allelic variants causing EE with deafness in three unrelated families. Agree the evidence is limited for the dominant deafness phenotype, but difficult to know whether to include the recessive phenotype in a 'non-syndromic HL' panel.
Created: 2 Jan 2020, 4:04 a.m. | Last Modified: 2 Jan 2020, 4:04 a.m.
Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy with deafness

Publications

Variants in this GENE are reported as part of current diagnostic practice

Anna de Burca (Genomics England Curator)

I don't know

Since reviewed by the ClinGen Hearing Loss Working Group in 2016, PMID:30237576 has reported a further case homozygous for a frameshift indel in DMXL2. The phenotype is described as GDD, epilepsy, macrocephaly, brain atrophy and dysmorphic facies, but hearing loss is not mentioned.
Created: 12 Feb 2019, 9:26 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polyendocrine-polyneuropathy syndrome; Deafness, autosomal dominant 71

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Rated amber to reflect the moderate evidence as assessed by the ClinGen group.
Created: 25 Jul 2017, 8:29 a.m.
ClinGen Gene Validity Classification Summary. Determined as MODERATE by calculated classification (dated: 12/19/2016) and MODERATE by Expert curation, Reviewed by the ClinGen Hearing Loss Working Group (dated 02/06/2017). Available here: https://search.clinicalgenome.org/kb/gene-validity/6237.
Created: 25 Jul 2017, 8:28 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Sensorineural Hearing Loss; ORPHA90636; OMIM:612186

Publications

Details

History Filter Activity

29 Jun 2020, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: DMXL2.

29 Jun 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: dmxl2 has been classified as Amber List (Moderate Evidence).

29 Jun 2020, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: DMXL2 were changed from Sensorineural Hearing Loss; ORPHA90636; OMIM:612186 to ?Deafness, autosomal dominant 71, 617605; Epileptic encephalopathy, early infantile, 81, 618663

29 Jun 2020, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: DMXL2 were set to 27657680; 22875945; 25248098

29 Jun 2020, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: DMXL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

25 Jul 2017, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for DMXL2 were set to 27657680; 22875945;25248098

25 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

25 Jul 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

DMXL2 was created by ellenmcdonagh

25 Jul 2017, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

DMXL2 was added to Congenital hearing impairment (profound/severe)panel. Sources: Other