Hereditary neuropathy or pain disorder

Gene: DHX9

Green List (high evidence)

Comment on phenotypes: This gene has now been associated with relevant phenotypes in OMIM (MIM #620988).

Created: 12 Mar 2025, 12:07 p.m. | Last Modified: 12 Mar 2025, 12:07 p.m.

Panel Version: 6.163

Comment on list classification: There is sufficient evidence available (three unrelated cases) for promoting this gene to green rating in the next major update.

Created: 28 Jul 2023, 5:31 p.m. | Last Modified: 28 Jul 2023, 5:31 p.m.

Panel Version: 3.44

PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder and three were reported with Charcot-Marie-Tooth disease (CMT). The three cases with CMT presented with adult-onset axonal neuropathy.

Created: 28 Jul 2023, 5:28 p.m. | Last Modified: 28 Jul 2023, 5:28 p.m.

Panel Version: 3.40

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Charcot-Marie-Tooth disease, MONDO:0015626

Publications

• 37467750

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 9:32 a.m. | Last Modified: 2 May 2024, 9:32 a.m.

Panel Version: 4.3

Comment on list classification: Rating this gene as Red, but with a watchlist tag, until more evidence is available.

Created: 25 Mar 2021, 11:46 a.m. | Last Modified: 25 Mar 2021, 11:46 a.m.

Panel Version: 1.25

Conference poster (Genomics of Rare Disease 2021) - 'DExH-box helicase 9 (DHX9) is a candidate hereditary axonal neuropathy gene' by Fatih et al, Baylor College of Medicine -

Report three unrelated individuals with adult-onset axonal neuropathy (age of onset: 41, 49, and 12 years old, respectively). Clinical features include limb weakness (3), muscle atrophy (2), diminished sensation in feet (2; plus in hands in 1 individual), ataxic gait (1), and painful neuropathy (1). All subjects exhibited neurogenic changes on EMG, and 2 cases also had normal or absent motor and sensory NCV.
Exome sequencing revealed distinct heterozygous variants in the DHX9 gene ([c.2537A>G, p.Asp846Gly]; [c.2510G>C, p.Arg837Thr]; [c.3763G>A, p.Ala1255Thr]). Segregation data was only available for one case, showing de novo occurrence. No functional data presented.

These variants have to be validated and currently DHX9 is deemed a candidate gene. No other publications in relation to this gene and phenotype are available in PubMed at this time.

Baylor College of Medicine POC: Dr. Daniel Calame, [email protected]
Sources: Other

Created: 25 Mar 2021, 11:45 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Adult-onset axonal neuropathy