Adult onset leukodystrophy

Gene: ANXA11

I don't know

Comment on list classification: There are three unrelated families reported with ANXA11 variants and white matter abnormalities - however, all three families were identified with the same variant. What matter abnormalities were not reported in successive studies. Hence, this gene should be rated amber with the current evidence.

Created: 30 Sep 2025, 5:16 p.m. | Last Modified: 30 Sep 2025, 5:16 p.m.

Panel Version: 6.7

Comment on phenotypes: This gene has been associated with relevant phenotypes in OMIM (MIM #619733). OMIM was accessed on 30 September 2025.

Created: 30 Sep 2025, 5:14 p.m. | Last Modified: 30 Sep 2025, 5:14 p.m.

Panel Version: 6.6

PMID:34048612 (2021) reported 11 patients from three different Brazilian families presenting with three different phenotypes - Amyotrophic lateral sclerosis (ALS), inclusion body myopathy (hIBM), and ALS + hIBM. The patients had proximal muscle weakness of the upper and lower limbs with walking difficulties, scapular winging, and abdominal weakness, suggestive of a limb-girdle type of myopathy. Brain imaging from patients showed white matter abnormalities using diffusion tensor imaging. All the affected probands shared the same missense variant (c.118G>T/ p.Asp40Tyr) from ANXA11 gene, suggesting it could be founder variant.

Although there were patients reported with variants affecting the Asp40 amino acid residue of ANXA11 gene and presenting with myopathy phenotype in successive studies (PMIDs: 36134701; 36651622; 40730020), there were no mentions of white matter abnormalities reported for these patients in these publications.
Sources: Literature

Created: 30 Sep 2025, 5:13 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Inclusion body myopathy and brain white matter abnormalities, OMIM:619733; inclusion body myopathy and brain white matter abnormalities, MONDO:0850514

Publications

• 34048612