Locus OPDM FAM193B

This is a newly proposed locus for OPDM, it does not have a type number yet and has not been validated. Oculopharyngodistal myopathy (OPDM) is a rare, adult-onset hereditary muscle disease. People with OPDM present with progressive eye and throat (pharyngeal) problems and involvement of the muscles of the lower legs and arms. Symptoms may include eyelid drooping (ptosis), swallowing difficulty, hoarse and nasal voice, leg and arm weakness, as well as muscle wasting in the face and in the legs and arms. Many people have respiratory problems due to respiratory muscle weakness. In rare cases, there is also hearing loss, as well as severe weakness in muscles of the forearms and thighs. As the disease progresses, other muscles may be affected. A blood exam may show an increased creatine kinase level and an abnormal EMG¹.

Prevalence

Found in two siblings in a UDN family^2,3.

Age of Onset

49-51 based on two siblings⁴.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr5:176981490-176981532

hg38 chr5:177554489-177554531

t2t chr5:178096748-178096792

Details

Benign range (<50) inferred from cohort data, but exact upper bound was not reported. Two affected patients had repeat lengths of 194 and 198, with an unaffected parent with a repeat length of 158⁴. The unaffected parent makes the inheritance pattern uncertain, but it appears to be autosomal dominant.

Mechanism

Accumulation of toxic RAN proteins is a proposed mechanism⁵

Detection

Year

2026⁴

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

GCC

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GCC

Pathogenic (gene)

CGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0025193

RExPRT: a machine learning tool to predict pathogenicity of tandem repeat loci.

Sarah,Fazal, Matt C,Danzi, Isaac,Xu, Shilpa Nadimpalli,Kobren, Shamil,Sunyaev, Chloe,Reuter, Shruti,Marwaha, Matthew,Wheeler, Egor,Dolzhenko, Francesca,Lucas, Stefan,Wuchty, Mustafa,Tekin, Stephan,Züchner, Vanessa,Aguiar-Pulido

Genome biology · 2024-01-31

pmid:38297326

Long-read sequencing for diagnosis of genetic myopathies.

Dennis,Yeow, Laura Ivete,Rudaks, Ryan,Davis, Karl,Ng, Roula,Ghaoui, Pak Leng,Cheong, Gianina,Ravenscroft, Marina,Kennerson, Ira,Deveson, Kishore Raj,Kumar

BMJ neurology open · 2025-05-11

pmid:40357124

Detailed tandem repeat allele profiling in 1,027 long-read genomes reveals genome-wide patterns of pathogenicity.

Matt C,Danzi, Isaac R L,Xu, Sarah,Fazal, Egor,Dolzhenko, David,Pellerin, Ben,Weisburd, Chloe,Reuter, Jacinda,Sampson, Chiara,Folland, Matthew,Wheeler, Anne,O'Donnell-Luria, Stefan,Wuchty, Gianina,Ravenscroft, Michael A,Eberle, Stephan,Zuchner

bioRxiv : the preprint server for biology · 2025-01-20

pmid:39868092

Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease.

Tanner D,Jensen, Bohan,Ni, Chloe M,Reuter, John E,Gorzynski, Sarah,Fazal, Devon,Bonner, Rachel A,Ungar, Pagé C,Goddard, Archana,Raja, Euan A,Ashley, Jonathan A,Bernstein, Stephan,Zuchner, Michael D,Greicius, Stephen B,Montgomery, Michael C,Schatz, Matthew T,Wheeler, Alexis,Battle

medRxiv : the preprint server for health sciences · 2024-03-26

pmid:38585781

Additional Literature

Additional literature related to this locus.