OPDM1_LRP12
- Gene
- LRP12
- Disease
- OPDM1
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 13
- Publications Reviewed
- 3
- Publication Span
- 2.59 years
- Last Updated
- 8/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Autosomal dominant oculopharyngodistal myopathy type 1 (OPDM1) is associated with a heterozygous noncoding CGG repeat expansion in the 5′ UTR of LRP12. The original discovery study identified LRP12 CGG expansions in OPDM probands and validated the locus by RP-PCR, Southern blotting, and control repeat-size analysis. A larger OPDM_LRP12 case series identified 65 Japanese patients from 59 families with 85–289 CGG repeats, supporting an inverse relationship between repeat size and age at onset and defining the phenotype as oculopharyngeal weakness with predominantly distal myopathy and rimmed vacuoles.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:31332380 | 6 | Study screened 17 familial and 17 sporadic OPDM probands with rimmed vacuoles after excluding PABPN1 and LOC642361/NUTM2B-AS1 expansions; LRP12 5′ UTR CGG expansions were confirmed by RP-PCR in 13/34 probands (5 familial, 8 sporadic). An additional 9/54 clinically similar probands without available biopsy also carried LRP12 expansions. |
| Collective Evidence | Allele | PMID:34047774 | 1 | In 60 OPDM_LRP12 patients, LRP12 CGG expansions ranged from 85 to 289 repeats; among 52 non-mosaic patients, repeat size showed a negative correlation with age at onset (r² = 0.188, P = .001). |
| Collective Evidence | Computational | PMID:31332380 | 0.5 | TRhist analysis of whole-genome sequencing identified a CGG expansion at chr8:104,588,973–104,588,999 in the LRP12 5′ UTR. Fragment analysis showed 13–45 repeat units in 998/1,000 controls, while 2/1,000 controls had expansions confirmed by RP-PCR and Southern blot. |
| Statistics | Case-control data | PMID:34047774 | 6 | Among 198 unrelated Japanese families/208 patients with suspected OPDM or OPMD after PABPN1 exclusion, LRP12 expansions were identified in 42 families with rimmed vacuoles and 17 families without biopsy; no LRP12 expansion was detected in 47 families without rimmed vacuoles. |
Experimental evidence
Total: 1
| Functional Alteration | Patient cells | PMID:35245110 | 1 |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.