Intranuclear Aggregates Precede Clinical Onset in Oculopharyngeal Muscular Dystrophy.

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• Oculopharyngeal muscular dystrophy (OPMD) is characterized by ptosis, dysphagia, and limb weakness.
• The role of intranuclear inclusions in OPMD pathophysiology remains unclear.

Purpose of the Study:

• To investigate the clinical and histopathological features of OPMD in a Dutch cohort.
• To examine presymptomatic carriers of the Ala-expanded-PABPN1 gene mutation.

Main Methods:

• Prospective observational study involving 40 OPMD patients and 18 adult children.
• Included structured history, neurological examination, muscle histology, and biochemical analysis.
• Autopsy was performed on one patient.

Main Results:

• Ptosis, dysphagia, limb girdle, and axial weakness were common OPMD symptoms.
• Intranuclear aggregates were present in presymptomatic carriers.
• Biochemical analysis showed no mitochondrial dysfunction in presymptomatic carriers.

Conclusions:

• Intranuclear aggregates form before clinical onset in OPMD due to Ala-expanded-PABPN1.
• Mitochondrial dysfunction may occur later in the disease progression.
• Limb girdle weakness is a frequent manifestation in Dutch OPMD patients.