Monogenic hearing loss
Gene: DMXL2
The rating and mode of inheritance 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: 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 biallelicCreated: 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
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
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
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
Tag for-review was removed from gene: DMXL2.
Phenotypes for gene: DMXL2 were changed from ?Deafness, autosomal dominant 71, 617605; Epileptic encephalopathy, early infantile, 81, 618663 to ?Deafness, autosomal dominant 71, OMIM:617605
Source Expert Review Green was added to DMXL2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag for-review tag was added to gene: DMXL2.
Gene: dmxl2 has been classified as Amber List (Moderate Evidence).
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
Publications for gene: DMXL2 were set to 27657680; 22875945; 25248098
Mode of inheritance for gene: DMXL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for DMXL2 were set to 27657680; 22875945;25248098
This gene has been classified as Amber List (Moderate Evidence).
DMXL2 was created by ellenmcdonagh
DMXL2 was added to Congenital hearing impairment (profound/severe)panel. Sources: Other