Curation OPDM1 LRP12

Gene LRP12
Disease OPDM1
Inheritance AD
Score

12 + 0 = 12 / 18

Genetic + experimental = total
Classification
0
18
Refuted
Moderate
Definitive
Last Updated 8/18/2025
Pubs Reviewed 2
Publication Span 1.92 years
Publication Interval 1.92 years
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.

All criTRia Curations Locus Page

Genetic evidence

Total: 12

Category
Type
Citation
Score
Details
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: 0

No experimental evidence details available.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.