Deafness_IsolatedAndComplex

Gene: DMXL2

Green List (high evidence)

RED for AD deafness, GREEN for AR in context of complex disorder.

Created: 8 Oct 2020, 10 p.m. | Last Modified: 8 Oct 2020, 10 p.m.

Panel Version: 1.2

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal dominant 71, MIM#617605; Epileptic encephalopathy, early infantile, 81, MIM# 618663

There's still no convincing evidence for AD inheritance:

- Chen 2017 (PMID:27657680): A heterozygous missense segregated with (AD) non-syndromic hearing loss in one Chinese family with multiple affected individuals. However, there are 9 heterozygotes in gnomADv2 for the missense variant. Authors only did functional studies in mouse and showed the gene is expressed in mouse cochlea. There were no variant-specific functional studies.


- Costain 2019 (PMID:30732576): Reported 3 patients with DD/ID or ASD, each patients were heterozygous for an intragenic loss of DMXL2 (inh not determined), an NMD-predicted SNV (maternally inherited) or a canonical splice variant (paternally inherited). No functional studies.

Created: 9 Sep 2020, 1:56 a.m. | Last Modified: 9 Sep 2020, 1:56 a.m.

Panel Version: 0.386

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 81, MIM#618663, Autosomal recessive

Publications

• 30732576
• 27657680

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

Green List (high evidence)

Moderate by ClinGen expert panel classification but single large family and functional studies only (AD). As a dominant cause of non syndromic deafness this gene is RED. Single paper with AR phenotype in 3 unrelated families - for the AR phenotype is GREEN.
Sources: Expert list

Created: 31 Dec 2019, 12:49 a.m. | Last Modified: 31 Dec 2019, 12:51 a.m.

Panel Version: 0.55

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autosomal dominant hearing loss; autosomal recessive EE with deafness

Publications

• 27657680
• 22875945
• 31688942