Autosomal dominant myopathy with rimmed ubiquitin-positive autophagic vacuolation (MRUPAV) is characterized by adult onset of slowly progressive skeletal muscle weakness variably affecting the distal or proximal lower limbs. Some patients may also have upper limb involvement or neck muscle weakness, but respiratory and bulbar involvement only rarely occurs. EMG studies show a myopathic process, and myotonia may also be observed¹. An early characterisation of the disease was reported in Blasi, et al.².

Prevalence

Studied in patients of chinese ancestry and two families of spanish ancestry^3,4.

Age of Onset

22-66^3,5,6,4.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr19:4510739-4513671

hg38 chr19:4510727-4513659

t2t chr19:4494212-4497342

Details

This is an expanded variable number tandem repeat (VNTR) in the PLIN4 gene, located in exon 3. This repeat consists of a 99 bp motif which encodes 33 amino-acids within the perilipin-4 protein⁷. Expansions of this 99 bp motif lead to insertion of multiple imperfect 33–amino acid repeats. These repetitive sequences are thought to contribute to abnormal protein aggregation and dysregulated autophagy seen in affected muscle tissue¹.

Mechanism

GoF

The present disease is characterized by dominantly inherited progressively increasing mobilization of aggrephagy at sites of progressive accumulation of a mutated protein, suggesting that the mutation is leading to aggregation, likely through misfolding, exceeding aggrephagic capacity⁷

Detection

Short-read sequencing and exome sequencing are reported to not reliably detect this repeat. Long-range PCR is used for detection, while long-read sequencing is used to fully resolve size and structure [@pmid:32451610; @pmid:33811808].

Year

2020⁷

Location in Gene

Coding Exon 3

Gene Strand

Alleles

Ref. Motif

TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC

Pathogenic (gene)

AAAGGAACCATCCAGACCGGCGTGGACACCAGTAAGACTGTCCTAACAGGTACCAAGGACACCGTCTGTAGTGGGGTGACTGGTGCCATGAATGTGGCC

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

References

Direct supporting references for info on this page.

1omim:601846

Abnormal lysosomal and ubiquitin-proteasome pathways in 19p13.3 distal myopathy.

Claudia,Di Blasi, Behzad,Moghadaszadeh, Claudia,Ciano, Tiziana,Negri, Alessio,Giavazzi, Ferdinando,Cornelio, Lucia,Morandi, Marina,Mora

Annals of neurology · 2004-07-01

pmid:15236412

Subsarcolemmal and cytoplasmic p62 positivity and rimmed vacuoles are distinctive for PLIN4-myopathy.

Qi,Wang, Meng,Yu, Wei,Zhang, Qiang,Gang, Zhiying,Xie, Jin,Xu, Chao,Zhou, Depeng,Wang, Lingchao,Meng, He,Lv, Zhirong,Jia, Jianwen,Deng, Yun,Yuan, Zhaoxia,Wang

Annals of clinical and translational neurology · 2022-09-24

pmid:36151849

Repeat Expansions in PLIN4 Cause Autosomal Dominant Vacuolar Myopathy With Sarcolemmal Features.

Laura,Llansó, Igor,Stevanovski, Germán,Morís, Roger,Collet-Vidiella, Alba,Segarra-Casas, Lidia,González-Quereda, Benjamín,Rodríguez-Santiago, Pia,Gallano, Rodrigo,Alvarez, Ana,Vesperinas, Rosa,Blanco, Beatriz,San-Millán, Carmen,Navarro, Isabel,Illa, Gianina,Ravenscroft, Ira W,Deveson, Eduard,Gallardo, Montse,Olivé

Annals of clinical and translational neurology · 2025-07-22

pmid:40693562

PLIN4-related myopathy: clinical, histological and imaging data in a large cohort of patients.

Lorenzo,Maggi, Sara,Gibertini, Eliana,Iannibelli, Annamaria,Gallone, Silvia,Bonanno, Daniele,Cazzato, Simonetta,Gerevini, Marco,Moscatelli, Flavia,Blasevich, Giorgia,Riolo, Renato,Mantegazza, Alessandra,Ruggieri

Journal of neurology · 2023-05-05

pmid:37145156

Expanding the phenotype and genotype spectra of PLIN4-associated myopathy with rimmed ubiquitin-positive autophagic vacuolation.

Kang,Yang, Yi-Heng,Zeng, Yu-Sen,Qiu, Feng,Lin, Hai-Zhu,Chen, Ming,Jin, Long,Chen, Fu-Ze,Zheng, Yuan-Liang,Ding, Chun-Yan,Cao, Min-Ting,Lin, Wan-Jin,Chen, Zhi-Qiang,Wang, Ning,Wang

Acta neuropathologica · 2022-05-02

pmid:35499779

Multiomic elucidation of a coding 99-mer repeat-expansion skeletal muscle disease.

Alessandra,Ruggieri, Sergey,Naumenko, Martin A,Smith, Eliana,Iannibelli, Flavia,Blasevich, Cinzia,Bragato, Sara,Gibertini, Kirston,Barton, Matthias,Vorgerd, Katrin,Marcus, Peixiang,Wang, Lorenzo,Maggi, Renato,Mantegazza, James J,Dowling, Rudolf A,Kley, Marina,Mora, Berge A,Minassian

Acta neuropathologica · 2020-05-25

pmid:32451610