Hereditary Neuropathy - complex

Gene: SETX

Green List (high evidence)

Bi-allelic variants are associated with spinocerebellar ataxia with axonal neuropathy-2, a neurodegenerative disorder characterised by juvenile onset of progressive cerebellar ataxia, axonal sensorimotor peripheral neuropathy, and increased serum alpha-fetoprotein (AFP; 104150). Oculomotor apraxia is a common but inconsistent finding, found in about 50% of patients; hence this disorder is sometimes referred to as 'ataxia-oculomotor apraxia-2' (AOA2).

Mono-allelic variants are associated with juvenile ALS, a chronic motor neuron disease characterised by combined upper and lower motor neuron symptoms and signs with onset before age 25 years.

Created: 30 Dec 2020, 5:56 a.m. | Last Modified: 30 Dec 2020, 5:56 a.m.

Panel Version: 0.94

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Amyotrophic lateral sclerosis 4, juvenile MIM# 602433; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 MIM# 606002

Green List (high evidence)

AD: missense mutations
AR: Null variants. Missense in biallelic form clustering in the N-terminal or helicase domains

Chen 2006: postulated LoF for AR condition but partial GoF for AD since heterozygote carriers of AOA2 are unaffected
Ma 2018/Orban 2007: postulated toxic or partial LoF with missense ALS4 since LoF in AOA2 causes a more widespread pathology

Created: 30 Dec 2020, 5:26 a.m. | Last Modified: 30 Dec 2020, 5:26 a.m.

Panel Version: 0.94

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Amyotrophic lateral sclerosis 4, juvenile MIM# 602433; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 MIM# 606002

Publications

• PMID: 23129421
• 16644229
• 30052327