Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese.
Hencher Han-Chih LeeShun WongBun ShengNin-Yuan Keith PanYing-Kit Frank LeungKwok-Kwong Dominic LauYue Sandy ChengLuen-Cheung HoRichard LiChi-Nam LeeTak-Hong TsoiYuk-Fai Nelson CheungYat-Pang Michael FuNim-Chi Amanda KanYim-Pui ChuWing-Chi Lisa AuHon-Ming Jonas YeungSiu-Hung LiChi-Fung Mark CheungHok-Fung TongLing-Yin Esther HungTina Yee-Ching ChanChi Terence LiTsz-Yan Tammy TongTin-Wing Candy TongHo-Ying Cory LeungKa-Ho LeeSung-Yan Sue YeungSau-Yin Blanka LeeTze-Chin Gene LauChing-Wan LamChloe Miu MakAlbert Yan-Wo ChanPublished in: Clinical genetics (2020)
FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC-related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty-six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two-thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late-onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone-based or antisense oligonucleotide strategies for this particular type of myopathy.