Hereditary neuropathy or pain disorder
Gene: DHX9
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
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: OtherCreated: 25 Mar 2021, 11:45 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Adult-onset axonal neuropathy
Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Tag watchlist was removed from gene: DHX9. Tag Q3_23_promote_green tag was added to gene: DHX9.
Phenotypes for gene: DHX9 were changed from Adult-onset axonal neuropathy to Adult-onset axonal neuropathy; Charcot-Marie-Tooth disease, MONDO:0015626
Publications for gene: DHX9 were set to
Mode of inheritance for gene: DHX9 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: dhx9 has been classified as Red List (Low Evidence).
gene: DHX9 was added gene: DHX9 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Other watchlist tags were added to gene: DHX9. Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DHX9 were set to Adult-onset axonal neuropathy