Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese.

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.

Single-nucleotide polymorphism of transient axonal glycoprotein-1 and its correlation with clinical features and prognosis in chronic inflammatory demyelinating polyneuropathy.

The single-nucleotide polymorphism (SNP) rs2275697 in the transient axonal glycoprotein-1 (TAG-1) gene was reported to be associated with responsiveness to intravenous immunoglobulin (IVIG) treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, it is not known if this SNP is associated with long-term prognosis. We examined the case records of 32 Chinese CIDP patients. The overall response rate to IVIG, prednisolone, or plasmapheresis was 83%. After 5.4 years, 57% of patients were on maintenance immunotherapy. Patients with higher modified Rankin score and more prolonged distal motor latencies in the upper limbs on presentation had a higher risk (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.23-12.11 and OR 1.04, 95% CI 1.01-1.07, respectively) of being on maintenance immunotherapy. Blood samples from 24 patients and 147 controls were examined for their genotypes of four non-synonymous SNPs (rs41264871, rs36074532, rs5611135, and rs2275697) in the coding region of TAG-1. The G allelic frequency of rs2275697 was similar between CIDP patients and controls (56% and 50%, respectively) and was not associated with treatment responsiveness, treatment dependence, disability, or mortality.