OPMD PABPN1

1/100,000 (population specific)³. Frequency of (GCN)11 alleles is 1-2% of North America/Europe/Japan⁴. Disease is found worldwide, in more than 30 countries⁴.

Age of Onset Details

Typical: 40-59⁵; Range: 20-79⁶.

Locus

hg19

chr14:23790681-23790711

hg38

chr14:23321472-23321502

t2t

chr14:17522488-17522518

Details

Disease is caused by a GCN polyalanine expansion in the first exon of PABPN1. Most known patients have (GCG)+, but GCN (any polyalanine) may be pathogenic⁴. This locus acts in a dominant manner for allele sizes ≥ 12 GCN motifs (90% of cases) and in a recessive manner for 11 GCN motifs, i.e. the genotype (GCN)11(GCN)11 (10% of cases). Additionally, disease is known to be more severe in cases of two expanded alleles. Age of onset is inverse to allele size, while penetrance and severity increase with allele size⁴. Mild, late-onset disease can occur in individuals with a (GCN)10(GCN)11 genotype, suggesting variable penetrance⁷. The definition of this locus differs in the literature with prior work counting exact GCG motifs for a benign size of (GCG)6⁸, while later resources count GCNs (any alanine codon), widening the region by 4 motifs to a benign size of (GCN)10^4,1. STRchive is using the GCN definition.

Mechanism

GoF/LoF

Polyalanine expansions leading to cellular toxicity (loss of function) as well as abnormal aggregation and inefficient protein degradation, which may impact mRNA processing⁴.

Year

1998⁸

Location in Gene

Exon 1

Gene Strand

Alleles

Ref. Motif

GCN

Pathogenic (ref.)

GCN

Pathogenic (gene)

CNG

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Repeat expansion disorders.

Zhongbo,Chen, Huw R,Morris, James,Polke, Nicholas W,Wood, Sonia,Gandhi, Mina,Ryten, Henry,Houlden, Arianna,Tucci

Practical neurology · 2024-09-30

pmid:39349043

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

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

Oculopharyngeal Muscular Dystrophy

Capucine,Trollet, Alexis,Boulinguiez, Fanny,Roth, Tanya,Stojkovic, Gillian,Butler-Browne, Teresinha,Evangelista, Jean,Lacau St Guily, Pascale,Richard

GeneReviews® · 1993-01-01

genereviews:NBK1126

Choked: A Case Report of Oculopharyngeal Muscular Dystrophy Mimicking Hypothyroidism From the Philippines.

Jerome M,Infante, Belinda Lioba,Nepomuceno

Cureus · 2023-06-27

pmid:37519616

Clinical and genetic features of a large homogeneous cohort of oculopharyngeal muscular dystrophy patients from the Canary Islands.

Jorge,Alonso-Pérez, Juan Carlos,de León Hernández, Helena,Pérez-Pérez, María Dolores,Mendoza-Grimón, Antonio José,Gutierrez-Martinez, Ioanna,Hadjigeorgiou, Fernando,Montón-Álvarez, Lidia,González-Quereda, Alicia,Alonso-Jimenez, Xavier,Suárez-Calvet, Jordi,Díaz-Manera

European journal of neurology · 2022-02-03

pmid:35112761

Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy.

Pascale,Richard, Capucine,Trollet, Tanya,Stojkovic, Alix,de Becdelievre, Sophie,Perie, Jean,Pouget, Bruno,Eymard

Neurology · 2016-12-23

pmid:28011929

Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy.

B,Brais, J P,Bouchard, Y G,Xie, D L,Rochefort, N,Chrétien, F M,Tomé, R G,Lafrenière, J M,Rommens, E,Uyama, O,Nohira, S,Blumen, A D,Korczyn, P,Heutink, J,Mathieu, A,Duranceau, F,Codère, M,Fardeau, G A,Rouleau

Nature genetics · 1998-02-01

pmid:9462747

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)

Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.

Alexis,Boulinguiez, Jamila,Dhiab, Barbara,Crisol, Laura,Muraine, Ludovic,Gaut, Corentin,Rouxel, Justine,Flaire, Hadidja-Rose,Mouigni, Mégane,Lemaitre, Benoit,Giroux, Lucie,Audoux, Benjamin,SaintPierre, Arnaud,Ferry, Vincent,Mouly, Gillian,Butler-Browne, Elisa,Negroni, Alberto,Malerba, Capucine,Trollet

Journal of cachexia, sarcopenia and muscle · 2024-08-07

pmid:39113268

Muscle MRI in Patients With Oculopharyngeal Muscular Dystrophy: A Longitudinal Study.

Rosemarie H M J M,Kroon, Johanna G,Kalf, Bert J M,de Swart, Linda,Heskamp, Jacky W J,de Rooy, Baziel G M,van Engelen, Corinne G C,Horlings

Neurology · 2023-12-14

pmid:38165364

Destabilizing Effect of Organo Ru(II) Salts on the Intermolecular Parallel CGG Repeat DNA Quadruplex Associated with Neurodegenerative/Neuromuscular Diseases.

Chakkarai,Sathyaseelan, Sabari,Veerapathiran, Uttam,Das, Gayathri,Ravichandran, Yogeeshwar,Ajjugal, Joginder,Singh, Aravind Kumar,Rengan, Thenmalarchelvi,Rathinavelan, Ganesan,Prabusankar

ACS chemical neuroscience · 2023-09-12

pmid:37698929

Oculopharyngeal muscular dystrophy mutations link the RNA-binding protein HNRNPQ to autophagosome biogenesis.

Hasan,Ishtayeh, Margarita,Galves, Tania T,Barnatan, Yevgeny,Berdichevsky, Fatima,Amer-Sarsour, Metsada,Pasmanik-Chor, Itzhak,Braverman, Sergiu C,Blumen, Avraham,Ashkenazi

Aging cell · 2023-08-09

pmid:37559347

Frequency and type of cancers in myotonic dystrophy: A retrospective cross-sectional study.

Eleonora S,D'Ambrosio, Kathy,Chuang, William S,David, Anthony A,Amato, Paloma,Gonzalez-Perez

Muscle & nerve · 2023-03-27

pmid:36790141

Muscle ultrasound is a sensitive biomarker in oculopharyngeal muscular dystrophy.

Rosemarie H M J M,Kroon, Johanna G,Kalf, Rutger L,Meijers, Bert J M,de Swart, Ian G M,Cameron, Jonne,Doorduin, Nens,van Alfen, Baziel G M,van Engelen, Corinne G C,Horlings

Muscle & nerve · 2022-08-12

pmid:35859342

Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy.

Masashi,Ogasawara, Nobuyuki,Eura, Utako,Nagaoka, Tatsuro,Sato, Hajime,Arahata, Tomohiro,Hayashi, Tomoko,Okamoto, Yuji,Takahashi, Madoka,Mori-Yoshimura, Yasushi,Oya, Akinori,Nakamura, Rui,Shimazaki, Terunori,Sano, Theerawat,Kumutpongpanich, Narihiro,Minami, Shinichiro,Hayashi, Satoru,Noguchi, Aritoshi,Iida, Masaki,Takao, Ichizo,Nishino

Neuropathology and applied neurobiology · 2021-12-28

pmid:34927285

A Japanese case of oculopharyngeal muscular dystrophy (OPMD) with PABPN1 c.35G > C; p.Gly12Ala point mutation.

Yo-Suke,Nishii, Yu-Ichi,Noto, Rei,Yasuda, Takamasa,Kitaoji, Shinji,Ashida, Eijirou,Tanaka, Narihiro,Minami, Ichizo,Nishino, Toshiki,Mizuno

BMC neurology · 2021-07-05

pmid:34225694

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