Population dependent; unknown percentage of LRP12 pathogenic variants. Typically East Asian ancestry²; potentially most frequent cause of OPDM in Japan³.

Age of Onset

Typical: 31-51³; Range: 7-66⁴.

HPO Terms

HP:0000218 High palate HP:0000407 Sensorineural hearing impairment HP:0000508 Ptosis HP:0000544 External ophthalmoplegia HP:0000597 Ophthalmoparesis HP:0001251 Ataxia HP:0001260 Dysarthria HP:0001284 Areflexia HP:0001288 Gait disturbance HP:0001324 Muscle weakness HP:0001337 Tremor HP:0001488 Bilateral ptosis HP:0001611 Hypernasal speech HP:0001618 Dysphonia HP:0001639 Hypertrophic cardiomyopathy HP:0001644 Dilated cardiomyopathy HP:0001824 Weight loss HP:0002015 Dysphagia HP:0002058 Myopathic facies HP:0002091 Restrictive ventilatory defect HP:0002098 Respiratory distress HP:0002460 Distal muscle weakness HP:0002500 Abnormal cerebral white matter morphology HP:0002747 Respiratory insufficiency due to muscle weakness HP:0002835 Aspiration HP:0003236 Elevated circulating creatine kinase activity HP:0003394 Muscle spasm HP:0003458 EMG: myopathic abnormalities HP:0003557 Increased variability in muscle fiber diameter HP:0003693 Distal amyotrophy HP:0003701 Proximal muscle weakness HP:0003736 Autophagic vacuoles HP:0003805 Rimmed vacuoles HP:0004757 Paroxysmal atrial fibrillation HP:0008756 Bowing of the vocal cords HP:0009027 Foot dorsiflexor weakness HP:0010628 Facial palsy HP:0012416 Hypercapnia HP:0012444 Brain atrophy HP:0032341 Reduced forced vital capacity HP:0100284 EMG: myotonic discharges

Association

Mendelian

Locus

hg19 chr8:105601198-105601227

hg38 chr8:104588970-104588999

t2t chr8:105716409-105716441

Details

Benign range (13-45) inferred from cohort data, but pathogenic range isn't yet fully understood⁵. In a cohort of 65 patients from 59 families, alleles ranged from 85-289 repeats, with an inverse relationship between size and age of onset³. Inherited peripheral neuropathy (IPN) may be associated with shorter expansions⁶. Interruptions seen: ACG, CCA⁷.

Mechanism

GoF?

RNA mediated toxicity hypothesized⁸; may involve RAN translation⁹. Somatic mosaicism and hypermethylation have also been reported¹⁰.

Detection

Short-read sequencing has been reported to be unreliable at detecting large expansions¹¹. RP-PCR followed by long-read sequencing is commonly used for characterization⁶.

Year

2019¹²

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)

–

gnomAD

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 · 2025-05-15

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

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

Prognosis of benign epilepsy of children with centro-temporal EEG foci.

K,Takahashi, M,Saito, K,Kyo, K,Gomibuchi, S,Niijima, H,Tada, T,Honda, Y,Sato, H,Takahashi, C,Ohtsuka

The Japanese journal of psychiatry and neurology · 1990-06-01

pmid:2124290

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Linking LRP12 CGG repeat expansion to inherited peripheral neuropathy.

Takahiro,Hobara, Masahiro,Ando, Yujiro,Higuchi, Jun-Hui,Yuan, Akiko,Yoshimura, Fumikazu,Kojima, Yutaka,Noguchi, Jun,Takei, Yu,Hiramatsu, Satoshi,Nozuma, Tomonori,Nakamura, Tadashi,Adachi, Keiko,Toyooka, Toru,Yamashita, Yusuke,Sakiyama, Akihiro,Hashiguchi, Eiji,Matsuura, Yuji,Okamoto, Hiroshi,Takashima

Journal of neurology, neurosurgery, and psychiatry · 2025-01-16

pmid:39013564

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.

Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson

Science advances · 2022-03-04

pmid:35245110

8omim:164310

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

Comparative Analysis of CRISPR/Cas9-targeted Nanopore Sequencing Approaches in Repeat Expansion Disorders.

Louise,Benarroch, Pierre-Yves,Boëlle, Hélène,Madry, Badreddine,Mohand Oumoussa, Nobuyuki,Eura, Ichizo,Nishino, Karim,Labrèche, Valeriia,Gorbunova, Guillaume,Bassez, Tanya,Stojkovic, Geneviève,Gourdon, Gisèle,Bonne, Stéphanie,Tomé

Genomics, proteomics & bioinformatics · 2025-10-22

pmid:41131788

11pmid:40858832

Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease.

Hiroyuki,Ishiura, Shota,Shibata, Jun,Yoshimura, Yuta,Suzuki, Wei,Qu, Koichiro,Doi, M Asem,Almansour, Junko Kanda,Kikuchi, Makiko,Taira, Jun,Mitsui, Yuji,Takahashi, Yaeko,Ichikawa, Tatsuo,Mano, Atsushi,Iwata, Yasuo,Harigaya, Miho Kawabe,Matsukawa, Takashi,Matsukawa, Masaki,Tanaka, Yuichiro,Shirota, Ryo,Ohtomo, Hisatomo,Kowa, Hidetoshi,Date, Aki,Mitsue, Hiroyuki,Hatsuta, Satoru,Morimoto, Shigeo,Murayama, Yasushi,Shiio, Yuko,Saito, Akihiko,Mitsutake, Mizuho,Kawai, Takuya,Sasaki, Yusuke,Sugiyama, Masashi,Hamada, Gaku,Ohtomo, Yasuo,Terao, Yoshihiko,Nakazato, Akitoshi,Takeda, Yoshio,Sakiyama, Yumi,Umeda-Kameyama, Jun,Shinmi, Katsuhisa,Ogata, Yutaka,Kohno, Shen-Yang,Lim, Ai Huey,Tan, Jun,Shimizu, Jun,Goto, Ichizo,Nishino, Tatsushi,Toda, Shinichi,Morishita, Shoji,Tsuji

Nature genetics · 2019-07-22

pmid:31332380

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)

Pathogenic CGG expansions in oculopharyngodistal myopathy exhibit distinct characteristics of each causative gene on the flanking sequences as well as methylation status.

Nobuyuki,Eura, Satoru,Noguchi, Megumu,Ogawa, Kyuto,Sonehara, Ai,Yamanaka, Takashi,Kurashige, Shinichiro,Hayashi, Yukinori,Okada, Kazuma,Sugie, Ichizo,Nishino

Genome medicine · 2026-03-27

pmid:41888971

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

A Family with Patients Manifesting Different Phenotypes of Neuromuscular Disease Depending on the CGG Repeat Number in LRP12.

Yohei,Iguchi, Koyo,Tsujikawa, Ayuka,Murakami, Kodai,Kume, Yuka,Nakazawa, Taichi,Oso, Yosuke,Nishio, Koji,Matsuo, Yuki,Fukami, Kunihiko,Araki, Tomoo,Ogi, Hideshi,Kawakami, Masahisa,Katsuno

Internal medicine (Tokyo, Japan) · 2025-10-23

pmid:41125376

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

Comparative Genotyping of Malaysian Clinical Isolates of

Nurul Asyikin,Abdul Rahman, AbdulRahman,Muthanna, Mohd Nasir Mohd,Desa, Nurul Diana,Dzaraly, Hazmin,Hazman, Nurshahira,Sulaiman, Norfazlina,Mohamad, Maitasha Alia Meor,Yahaya, Mazen M,Jamil Al-Obaidi, Niazlin,Mohd Taib, Siti Norbaya,Masri

The Malaysian journal of medical sciences : MJMS · 2025-02-28

pmid:40417202

A case report of oculopharyngodistal myopathy with 126 CGG repeat expansions in

Wenjing,Wang, Tielun,Yin, Xinyu,Zhang, Zhaoxia,Wang, Tianyun,Wang, Shuo,Zhang, Yingshuang,Zhang, Dongsheng,Fan

Frontiers in genetics · 2025-02-27

pmid:40084170

Short tandem repeat expansions in

Lyndal,Henden, Liam G,Fearnley, Dean,Southwood, Andrew,Smith, Dominic B,Rowe, Matthew C,Kiernan, Roger,Pamphlett, Melanie,Bahlo, Ian P,Blair, Kelly L,Williams

Amyotrophic lateral sclerosis & frontotemporal degeneration · 2024-05-10

pmid:38726482

Non-coding CGG repeat expansion in

Xinyu,Gu, Jiaxi,Yu, Kexin,Jiao, Jianwen,Deng, Xingyu,Xia, Kai,Qiao, Dongyue,Yue, Mingshi,Gao, Chongbo,Zhao, Jihong,Dong, Gongchun,Huang, Jingli,Shan, Chuanzhu,Yan, Li,Di, Yuwei,Da, Wenhua,Zhu, Jianying,Xi, Zhaoxia,Wang

Journal of medical genetics · 2024-03-21

pmid:37923380

A large pedigree study confirmed the CGG repeat expansion of RILPL1 Is associated with oculopharyngodistal myopathy.

Xinzhuang,Yang, Dingding,Zhang, Si,Shen, Pidong,Li, Mengjie,Li, Jingwen,Niu, Dongrui,Ma, Dan,Xu, Shuangjie,Li, Xueyu,Guo, Zhen,Wang, Yanhuan,Zhao, Haitao,Ren, Chao,Ling, Yang,Wang, Yu,Fan, Jianxiong,Shen, Yicheng,Zhu, Depeng,Wang, Liying,Cui, Lin,Chen, Changhe,Shi, Yi,Dai

BMC medical genomics · 2023-10-20

pmid:37864208

Locus OPDM1 LRP12

Disease

Locus

Alleles

gnomAD

References

Additional Literature