Abstract Details

Title Myofibrillar Myopathy 5: Clinical, Morphological and Genetic Studies of a Cohort of Chinese Patients with Novel Pathogenic FLNC Nonsense Mutation

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P9 - Poster Session 9 (12:00 PM-1:00 PM)

Poster/Presentation
Number 1-013

Objective To understand the clinical, morphological and genetic characteristics of myofibrillar myopathy type 5 in Chinese populations.

Background Myofibrillar myopathy type 5 (MFM5) is a rare autosomal dominant genetic myopathy caused by mutation of FLNC gene encoding filamin-C that helps in maintaining myofibril assembly, remodeling and maintenance. The clinical manifestation of MFM5 varies corresponding to the difference of FLNC mutation types and locations. Although myofibrillar myopathy can be characteristically recognized by muscle histopathological analyses, the precise molecular etiology cannot be readily discerned without genetic testing. Although series of myofibrillar myopathy cohorts have been reported in American , German, Italian and French populations, no Chinese population cohort data is currently available.

Design/Methods

Forty myofibrillar myopathy type 5 subjects from five Chinese families were identified; Clinical manifestations were summarized; Magnetic resonance imaging (MRI) pelvis, thigh and leg images were obtained for pattern description. Histopathological analyses were performed. Next-generation sequencing (NGS) was utilized for molecular diagnosis.

Results Majority of MFM5 patients had symptoms onset over 40 years old. Weakness of lower limb proximal muscles was firstly presented, and it progressed slowly to affect both distal and upper limb muscles. Large fiber axonal peripheral neuropathy, restrictive lung disease and cardiac dysfunction were observed among them. They exhibited consistent MRI muscle pattern and characteristic histopathological findings. Genetic testing detected a novel FLNC c.8129G>A mutation at dimerization domain of filamin-C.

Conclusions

This is the first and the largest myofibrillar myopathy type 5 cohort in Chinese population. A novel FLNC c.8129G>A mutation was identified. The clinical, morphological, radiological findings of this disease entity was characteristic. Recurrent presence of this FLNC nonsense mutation among different unrelated families implied its founder effect among Chinese populations. Understanding the clinical, morphological and genetic characteristics of MFM5 in Chinese populations helped in early recognition and diagnosis of the disease, understanding disease mechanisms and promoting exploration of potential therapeutics.

Authors/Disclosures
Yuan Gao, MD, PhD, MRCP (Division of Neurology, Dept. of Medicine) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Windsor Mak	No disclosure on file
	No disclosure on file
	No disclosure on file
Shu Leong Ho, MD, F�鶹��ýӳ�� (Gleneagles Hospital Hong Kong)	No disclosure on file

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