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Updated: Jun 12, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
CGG/CCG Repeat Expansions in LOC642361/NUTM2B-AS1 in Thai Patients With Oculopharyngodistal Myopathy
Sunsanee Pongpakdee1, Metha Apiwattanakul1, Thanes Termglinchan1
1From the Department of Medicine (S.P.), Bhumibol Adulyadej Hospital; Department of Neurology (M.A., T.T.), Neurological Institute of Thailand; Department of Medicine (R.W., C.D.), Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok; Department of Medicine (T.L.), HRH Princess Sirindhorn Hospital, Rayong; Department of Radiology (S.W.), Bhumibol Adulyadej Hospital, Bangkok, Thailand; Department of Neuromuscular Research (A.Y., I.N.), National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP); and Department of Clinical Genome Analysis (S.F., A.I., I.N.), Medical Genome Center, NCNP, Tokyo, Japan.
Insights
This study links CGG/CCG repeat expansion in LOC642361/NUTM2B-AS1 to oculopharyngodistal myopathy (OPDM). The findings highlight OPDM as the primary manifestation, with variable leukoencephalopathy in affected individuals.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Oculopharyngodistal myopathy (OPDM) is a rare neuromuscular disorder.
- Genetic factors are implicated in the pathogenesis of various myopathies.
- Previous studies suggested a link between leukoencephalopathy and oculopharyngeal myopathy.
Purpose of the Study:
- To characterize oculopharyngodistal myopathy (OPDM) in Thai patients.
- To investigate the role of CGG/CCG repeat expansion in LOC642361/NUTM2B-AS1 in OPDM.
- To differentiate OPDM from oculopharyngeal myopathy with leukoencephalopathy (OPML).
Main Methods:
- Repeat-primed PCR was used to analyze CGG/CCG repeat sizes in LOC642361/NUTM2B-AS1.
- Clinical data from four Thai patients with suspected OPDM were reviewed.
- Clinicopathologic features and genetic findings were correlated.
Main Results:
- All four patients exhibited somatic instability of expanded CGG/CCG repeats.
- Oculopharyngeal weakness was the primary clinical manifestation.
- Electrophysiologic evidence of distal myopathy was observed, even without limb weakness.
- Leukoencephalopathy was variably present or absent across patients.
Conclusions:
- CGG/CCG repeat expansion in LOC642361/NUTM2B-AS1 is strongly associated with oculopharyngodistal myopathy (OPDM).
- OPDM, rather than OPML, appears to be the predominant phenotype linked to this genetic expansion.
- The variable presence of leukoencephalopathy supports OPDM as the primary clinical outcome.
Objectives:
This study characterizes oculopharyngodistal myopathy in 4 Thai patients from 3 families with CGG/CCG repeat expansion in LOC642361/NUTM2B-AS1.
Methods:
Repeat-primed PCR analyzed CGG/CCG repeat size in LOC642361/NUTM2B-AS1 in 4 Thai patients suspected of oculopharyngodistal myopathy (OPDM). Clinical records were reviewed for clinicopathologic features.
Results:
All patients exhibited strong somatic instabilities of the expanded CGG/CCG repeats, primarily manifesting as oculopharyngeal weakness. Patient 1 had mild finger extensor and intrinsic hand muscle weakness, and although patient 2 lacked limb weakness, both siblings showed electrophysiologic evidence of distal myopathy, indicative of OPDM. Patient 3, the daughter of a sibling with OPDM reported in 2004, lacked limb weakness or leukoencephalopathy on brain MRI. Patient 4, initially misdiagnosed with refractory myasthenia gravis, had generalized muscle weakness.
Discussion:
While initially characterized as oculopharyngeal myopathy with leukoencephalopathy (OPML) in a Japanese family, our study suggests a stronger association between CGG/CCG expansion in LOC642361/NUTM2B-AS1 and oculopharyngodistal myopathy (OPDM) rather than OPML. The variable presence or absence of leukoencephalopathy further supports OPDM as the predominant clinical manifestation linked to CGG/CCG expansion in LOC642361/NUTM2B-AS1.
