Locus OPDM5 ABCD3

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 individuals of European, Japanese, and Chinese ancestry^2,3.

Age of Onset

Typical: 24-30; Range: 10-50⁴. Age of onset data is limited to 8 families.

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:0008997 Proximal upper limb 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:0010550 Paraplegia 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 HP:3000010 Abnormality of orbicularis oris muscle

Association

Mendelian

Locus

hg19 chr1:94883977-94884000

hg38 chr1:94418421-94418444

t2t chr1:94266544-94266567

Details

Characterized in eight unrelated families which were used to establish benign (3-44) and pathogenic (118-694) ranges⁴.

Mechanism

Potentially over-expression of transcripts⁴.

Detection

RP-PCR has been used for detection⁴. Short-read sequencing has significantly underestimated repeat count, while long-read sequencing has accurately resolved size⁴.

Year

2023⁴

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

CCG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CCG

Pathogen. (gene)

CCG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0025193

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis.

Elisa,Vegezzi, Hiroyuki,Ishiura, D Cristopher,Bragg, David,Pellerin, Francesca,Magrinelli, Riccardo,Currò, Stefano,Facchini, Arianna,Tucci, John,Hardy, Nutan,Sharma, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Mary M,Reilly, Shoji,Tsuji, Henry,Houlden, Andrea,Cortese

The Lancet. Neurology · 2024-07-01

pmid:38876750

Clinicopathologic Features of Oculopharyngodistal Myopathy With LRP12 CGG Repeat Expansions Compared With Other Oculopharyngodistal Myopathy Subtypes.

Theerawat,Kumutpongpanich, Masashi,Ogasawara, Ayami,Ozaki, Hiroyuki,Ishiura, Shoji,Tsuji, Narihiro,Minami, Shinichiro,Hayashi, Satoru,Noguchi, Aritoshi,Iida, Ichizo,Nishino, Madoka,Mori-Yoshimura, Yasushi,Oya, Kenjiro,Ono, Toshio,Shimizu, Akihiro,Kawata, Shun,Shimohama, Keiko,Toyooka, Kaoru,Endo, Shuta,Toru, Oga,Sasaki, Kenji,Isahaya, Masanori P,Takahashi, Kazuo,Iwasa, Jun-Ichi,Kira, Tatsuya,Yamamoto, Michi,Kawamoto, Tadanori,Hamano, Kazuma,Sugie, Nobuyuki,Eura, Tomo,Shiota, Mizuho,Koide, Kanako,Sekiya, Hideaki,Kishi, Takuto,Hideyama, Shigeru,Kawai, Satoshi,Yanagimoto, Hiroyasu,Sato, Hajime,Arahata, Shigeo,Murayama, Kayoko,Saito, Hideo,Hara, Takashi,Kanda, Hiroshi,Yaguchi, Noboru,Imai, Yuichi,Kawagashira, Mitsuru,Sanada, Kazuki,Obara, Misako,Kaido, Minori,Furuta, Takashi,Kurashige, Wataru,Hara, Daisuke,Kuzume, Mamoru,Yamamoto, Jun,Tsugawa, Hitaru,Kishida, Naoki,Ishizuka, Kohei,Morimoto, Yukio,Tsuji, Atsuko,Tsuneyama, Atsuhiro,Matsuno, Ryo,Sasaki, Daigo,Tamakoshi, Erika,Abe, Shinichiro,Yamada, Akiyuki,Uzawa

JAMA neurology · 2021-07-01

pmid:34047774

A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry.

Andrea,Cortese, Sarah J,Beecroft, Stefano,Facchini, Riccardo,Curro, Macarena,Cabrera-Serrano, Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, Ben,Weisburd, Chiara,Folland, Gavin,Monahan, Carolin K,Scriba, Lein,Dofash, Mridul,Johari, Bianca R,Grosz, Melina,Ellis, Liam G,Fearnley, Rick,Tankard, Justin,Read, Ashirwad,Merve, Natalia,Dominik, Elisa,Vegezzi, Ricardo P,Schnekenberg, Gorka,Fernandez-Eulate, Marion,Masingue, Diane,Giovannini, Martin B,Delatycki, Elsdon,Storey, Mac,Gardner, David J,Amor, Garth,Nicholson, Steve,Vucic, Robert D,Henderson, Thomas,Robertson, Jason,Dyke, Vicki,Fabian, Frank,Mastaglia, Mark R,Davis, Marina,Kennerson, Ros,Quinlivan, Simon,Hammans, Arianna,Tucci, Melanie,Bahlo, Catriona A,McLean, Nigel G,Laing, Tanya,Stojkovic, Henry,Houlden, Michael G,Hanna, Ira W,Deveson, Paul J,Lockhart, Phillipa J,Lamont, Michael C,Fahey, Enrico,Bugiardini, Gianina,Ravenscroft

Nature communications · 2024-07-27

pmid:39068203

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

A 5' UTR CCG expansion in

Liedewei,Van de Vondel, Riccardo,Curro, Stefano,Facchini, Isaac R L,Xu, Jonathan,De Winter, Ilaria,Quartesan, Alice,Monticelli, Alicia,Alonso-Jimenez, Willem,De Ridder, Alessandro,Bertini, Gustavo,Alves, Francesca,Pizzuto, Hermione,Ugolini, David,Pellerin, Tim,De Pooter, Ashirwad,Merve, Pedro,Machado, Lydia,Sagath, Kornelia,Neveling, Alexander,Hoischen, Michael G,Hanna, Robert D S,Pitceathly, Henry,Houlden, Arianna,Tucci, Enrico,Bugiardini, Stefen,Brady, Mark,Roberts, Matt C,Danzi, Stephan,Züchner, Jonathan,Baets, Andrea,Cortese

medRxiv : the preprint server for health sciences · 2026-04-01

pmid:41959811

Translation of expanded CGG repeats in LRP12 associated oculopharyngodistal myopathy.

Chengcheng,Li, Jil A,Daw, Sara K,Pittman, Connor J,Maltby, Hidetoshi,Sakurai, Peter K,Todd, Conrad C,Weihl

Acta neuropathologica communications · 2026-03-06

pmid:41792844

CGG repeat expansions in Charcot-Marie-Tooth disease: insights from the 100 000 Genomes Project.

Alessandro,Bertini, Stefano,Facchini, Ilaria,Quartesan, Riccardo,Currò, Ricardo Parolin,Schnekenberg, Natalia,Dominik, Gustavo,Alves, Lucia,Ferullo, Arianna,Tucci, Henry,Houlden, Mary M,Reilly, Andrea,Cortese

Journal of neurology, neurosurgery, and psychiatry · 2026-05-14

pmid:40645757