Oculopharyngodistal myopathy: already 3 genes identified

 

Oculopharyngodistal myopathy (OPDM) and oculopharyngeal muscular dystrophy (OPMD) are due to a a repeat expansion of triplets. OPDM is much rarer than DMOP and is distinguished by the topography of muscle involvement in the limbs and the genes involved. In oculopharyngeal muscular dystrophy, the muscle damage is proximal and the abnormality involves the PABPN1 gene (GCG triplet). In oculopharyngeal-distal myopathy, muscle involvement is distal and three genes are involved to date: the LRP12, GIPC1 or NOTCH2NLC genes (CGG triplet). 

  • Analysis of the LRP12 and GIPC1 genes from a cohort of 41 Chinese patients with OPDM shows that 28 of them had abnormalities in the GIPC1 gene and 1 in the LRP12 gene. 
  • The involvement of the NOTCH2NLC gene was demonstrated by a Japanese team which specifically focused on abnormalities in this gene in a cohort of 211 patients with OPMD or OPDM. The NOTCH2NLC gene was chosen because it is involved in the disease of neuronal intranuclear inclusion disease (NIID), a genetic disease that has some features in common with OPDM (muscle weakness, dysarthria, dysphagia). This approach had previously made it possible to discover the involvement of the LRP12 gene in OPDM. Seven people with OPDM had an abnormality in the NOTCH2NLC gene. Note that they also had certain symptoms suggestive of NIID such as leukoencephalopathy or retinal degeneration …
  • In a Chinese study whose results were published in March 2021, in a Chinese cohort of 24 people with OPDM, there were 4 people with abnormalities in the NOTCH2NLC gene, 1 person with abnormalities on LRP12 and 12 people with abnormalities in the GIPC1 gene.

Other genes are yet to be discovered. 

 

5′ UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy. Xi J, Wang X, Yue D, Dou T, Wu Q, Lu J, Liu Y, Yu W, Qiao K, Lin J, Luo S, Li J, Du A, Dong J, Chen Y, Luo L, Yang J, Niu Z, Liang Z, Zhao C, Lu J, Zhu W, Zhou Y. Brain. 2020 Dec 29:

 

CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations. Ogasawara M, Iida A, Kumutpongpanich T, Ozaki A, Oya Y, Konishi H, Nakamura A, Abe R, Takai H, Hanajima R, Doi H, Tanaka F, Nakamura H, Nonaka I, Wang Z, Hayashi S, Noguchi S, Nishino I. Acta Neuropathol Commun. 2020 Nov 25

 

The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3. Yu J, Deng J, Guo X, Shan J, Luan X, Cao L, Zhao J, Yu M, Zhang W, Lv H, Xie Z, Meng L, Zheng Y, Zhao Y, Gang Q, Wang Q, Liu J, Zhu M, Zhou B, Li P, Liu Y, Wang Y, Yan C, Hong D, Yuan Y, Wang Z. Brain. 2021 Mars