Hereditary neuropathy or pain disorder

Gene: SCO2

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 6:06 p.m. | Last Modified: 10 Oct 2023, 6:06 p.m.

Panel Version: 3.58

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: This gene should be rated GREEN as there are four unrelated cases identified with CMT type 4 (axonal polyneuropathy).

Created: 4 Mar 2023, 4:39 p.m. | Last Modified: 4 Mar 2023, 4:39 p.m.

Panel Version: 2.25

As reviewed by Zornitza Stark, PMID:29351582 reported two unrelated cases with compound heterozygous variants in SCO2 gene (p.Glu140Lys/ p.Pro169Thr and p.Asp135Gly/ p.Arg171Gln). These two patients presented with axonal polyneuropathy (Charcot-Marie-Tooth disease type 4). They developed predominantly motor neuropathy, survived infancy, and have not yet developed the cardiomyopathy that causes death in early infancy in previously reported patients associated with Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377).

PMID:31844624 reported two siblings with homozygous missense variant in SCO2 gene (p.Arg255Trp) who presented with cerebellar ataxia, progressive peripheral axonal neuropathy and long survival. Similarly, homozygous variant p.Gly121Arg was identified in two brothers in PMID:35112411 and they were reported with axonal motor neuropathy like the other cases.

Autosomal recessive variants in this gene have been associated with Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377) in OMIM and Gene2Phenotype, which primarily has a cardiac phenotype. The axonal neuropathy phenotype without cardiac presentation has not yet been recorded in these resources.

Created: 4 Mar 2023, 4:34 p.m. | Last Modified: 4 Mar 2023, 4:34 p.m.

Panel Version: 2.22

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Charcot-Marie-Tooth disease type 4, MONDO:0018995; Mitochondrial complex IV deficiency, nuclear type 2, OMIM:604377

Publications

• 29351582
• 31844624
• 35112411

I don't know

Two unrelated cases with compound heterozygous variants and a CMT phenotype. Cardiomyopathy not present.
Sources: Expert list

Created: 2 Apr 2020, 7:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
axonal Charcot-Marie-Tooth disease

Publications

• 29351582