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

HP:0000183 Tongue muscle weakness HP:0000218 High palate HP:0000301 Abnormality of facial musculature HP:0000408 Progressive sensorineural hearing impairment HP:0000590 Progressive external ophthalmoplegia HP:0000597 Ophthalmoparesis HP:0001284 Areflexia HP:0001288 Gait disturbance HP:0001604 Vocal cord paresis HP:0001824 Weight loss HP:0002058 Myopathic facies HP:0002091 Restrictive ventilatory defect HP:0002100 Recurrent aspiration pneumonia HP:0002505 Loss of ambulation HP:0002705 High, narrow palate HP:0002747 Respiratory insufficiency due to muscle weakness HP:0007149 Distal upper limb amyotrophy HP:0007838 Progressive ptosis HP:0008376 Nasal dysarthria HP:0008756 Bowing of the vocal cords HP:0008944 Distal lower limb amyotrophy HP:0008959 Distal upper limb muscle weakness HP:0008963 Tibialis muscle weakness HP:0009027 Foot dorsiflexor weakness HP:0009053 Distal lower limb muscle weakness HP:0009063 Progressive distal muscle weakness HP:0009073 Progressive proximal muscle weakness HP:0030192 Fatigable weakness of bulbar muscles HP:0030319 Weakness of facial musculature HP:0031162 Impaired oropharyngeal swallow response HP:0200136 Oral-pharyngeal dysphagia HP:0430015 Abnormal morphology of musculature of pharynx HP:3000005 Abnormality of masseter muscle

Association

Mendelian

Locus

hg19chr5:176981490-176981532

hg38chr5:177554489-177554531

t2tchr5:178096748-178096792

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. An expansion of 675 repeats was identified in an unaffected individual who had hypermethylation with transcriptional silencing, which indicates that hypermethylation may be protective⁵.

Mechanism

Accumulation of toxic RAN proteins is a proposed mechanism⁶.

Detection

Year

2026⁴

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

CCG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CCG

Pathogen. (gene)

CGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (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

5pmid:42326780

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.