Hereditary neuropathy or pain disorder
Gene: DHTKD1
Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.Created: 23 Aug 2023, 8:03 p.m. | Last Modified: 23 Aug 2023, 8:03 p.m.
Panel Version: 3.52
PMID:23141294 - Eight individuals from a 5-generation Chinese family were reported with Charcot-Marie-Tooth disease (CMT2) and heterozygous nonsense variant (p.Tyr485Ter) in the DHTKD1 gene.
PMID:28902413 - In this large cohort of 612 patients with hereditary neuropathies, one patient was identified with a monoallelic DHTKD variant.
PMID:34571524 - A 10 year-old male patient was reported with obesity, frequent falls, swollen legs and thighs, and pain in the lower and upper limbs. He was identified with heterozygous variants in DHTKD1 (associated with CMT2Q) and NTRK2 (associated with obesity, hyperphagia, and developmental delay).
PMID:29661920 - Studies on mouse models showed that Dhtkd1-/- mice mimic the major aspects of CMT2 phenotypes, characterized by progressive weakness and atrophy in the distal parts of limbs with motor and sensory dysfunctions, which are accompanied with decreased nerve conduction velocity.
Autosomal dominant variants in DHTKD1 gene has been associated with CMT2Q in OMIM (MIM #615025), but not yet associated with any phenotypes in Gene2Phenotype.Created: 23 Aug 2023, 8:01 p.m. | Last Modified: 23 Aug 2023, 8:01 p.m.
Panel Version: 3.48
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Charcot-Marie-Tooth disease, axonal, type 2Q, OMIM:615025
Publications
One multigenerational family reported plus another individual in a large CMT cohort; animal model. The variant reported in the Chinese family has been reported x1 gnomad, which does not necessarily make it 'benign'. Having said that, the gene is not constrained for LoF variants.Created: 31 Mar 2020, 8:58 a.m. | Last Modified: 31 Mar 2020, 8:58 a.m.
Panel Version: 1.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Charcot-Marie-Tooth disease, axonal, type 2Q, MIM#615025
Publications
Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.Created: 29 Apr 2019, 12:53 p.m.
Unable to find any evidence of clear neuropathy associationCreated: 29 Apr 2019, 12:30 p.m.
Phenotypes
Charcot Marie Tooth disease, axonal, type 2Q, 615025; 2 aminoadipic 2 oxoadipic aciduria, 204750
Variants in this GENE are reported as part of current diagnostic practice
only a single heterozygous nonsense mutation has been reorted in a large Chinese pedigreeCreated: 9 Dec 2015, 4:47 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Remove from panel, only single mutation reported was a non-sense mutation but this has been reported as a benign polymorphism in the heterozygous state.Created: 9 Dec 2015, 8:49 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Remove from panel, only single mutation reported was a non-sense mutation but this has been reported as a benign polymorphism in the heterozygous state.Created: 8 Dec 2015, 3:05 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: dhtkd1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: DHTKD1 were changed from Charcot Marie Tooth disease, axonal, type 2Q, 615025; 2 aminoadipic 2 oxoadipic aciduria, 204750 to ?Charcot-Marie-Tooth disease, axonal, type 2Q, OMIM:615025
Publications for gene: DHTKD1 were set to
Mode of inheritance for gene: DHTKD1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q3_23_promote_green tag was added to gene: DHTKD1.
gene: DHTKD1 was added gene: DHTKD1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,South West GLH,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: DHTKD1 was set to Phenotypes for gene: DHTKD1 were set to Charcot Marie Tooth disease, axonal, type 2Q, 615025; 2 aminoadipic 2 oxoadipic aciduria, 204750