Hereditary neuropathy or pain disorder

Gene: TTC19

Green List (high evidence)

Comment on list classification: As reviewed by Alexander Rossor, there are three unrelated patents reported with biallelic TTC19 variants and motor neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 30 Sep 2025, 10:28 a.m. | Last Modified: 30 Sep 2025, 10:28 a.m.

Panel Version: 7.11

Comment on phenotypes: This gene has been associated with relevant phenotype in both OMIM (MIM #615157, OMIM accessed on 30 September 2025) and Gene2Phenotype (with 'definitive' rating on the DD panel).

Created: 30 Sep 2025, 10:27 a.m. | Last Modified: 30 Sep 2025, 10:27 a.m.

Panel Version: 7.10

PMID:25652355 (2015) reported a 27-year-old male patient of Japanese descent with cerebellar ataxia, spastic paraparesis, loss of deep sensation, mild frontal lobe dysfunction and transient psychiatric symptoms. The patient was identified with a novel homozygous frameshift variant (p.Pro54Alafs*48) in TTC19. Motor axonal neuropathy of the lower extremities, but no apparent sensory neuropathy was detected via nerve conduction studies.

PMID:37927170 (2024) reported a 13-year-old male patient of Chinese descent with basal ganglia involvement, manifested with progressive movement disorders, limb weakness, suspicious ataxia, and peripheral neuropathy. This patient was identified with a homozygous TTC19 variant (p.p.Leu240Serfs*17). Electrophysiology showed chronic neurogenic lesions on the extremities. The motor and sensory fibers of both lower limbs were impaired. The motor fibers were the most affected in the lower limbs, especially neurogenic lesions in the proximal left tibial nerve.

PMID:40946707 (2025) reported a male patient of Malian descent presenting with cerebellar ataxia and attention deficits from early childhood. During adolescence, he developed additional features including dysarthria, dysphagia, dysexecutive syndrome, and signs of peripheral motor neuropathy. Neurophysiological studies confirmed a diffuse, axonal, pure distal motor neuropathy. The patient was identified with a novel homozygous nonsense variant in TTC19 gene (p.Gly79Ter).

Created: 30 Sep 2025, 10:25 a.m. | Last Modified: 30 Sep 2025, 10:25 a.m.

Panel Version: 7.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex III deficiency, nuclear type 2, OMIM:615157; mitochondrial complex III deficiency nuclear type 2, MONDO:0014063

Publications

• 25652355
• 37927170
• 40946707

Green List (high evidence)

Evidence of motor axonal neuropathy in 3 unrelated individuals.
Sources: Expert list

Created: 21 Sep 2025, 10:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ataxia; apraxia; dystonia; dysarthria; necrotic brain lesions; motor axonal neuropathy

Publications

• 40946707
• 37927170
• 25652355