Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129GA in Hong Kong Chinese
| Autor: | Han-Chih Hencher Lee, TH Tsoi, Shun Wong, Ying-Kit Frank Leung, Tina Yee-Ching Chan, Chloe Miu Mak, Tze-Chin Gene Lau, Hok-Fung Tong, Bun Sheng, Richard Li, Chi-Nam Lee, Ka-Ho Lee, Luen-Cheung Ho, Ling-Yin Esther Hung, Tin-Wing Tong, Yuk-Fai Nelson Cheung, Yim-Pui Chu, Ching-Wan Lam, Yue Sandy Cheng, Siu-Hung Li, Chi Terence Li, Nin-Yuan Keith Pan, Albert Yan-Wo Chan, Nim-Chi Amanda Kan, Yat-Pang Michael Fu, Kwok-kwong Lau, Sung-Yan Sue Yeung, Ho-Ying Cory Leung, Hon-Ming Jonas Yeung, Chi-Fung Mark Cheung, Wing-Chi Lisa Au, Sau-Yin Blanka Lee, Tsz-Yan Tammy Tong |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Filamins 030105 genetics & heredity 03 medical and health sciences Asian People Internal medicine Genetics Medicine Humans Progressive proximal muscle weakness FLNC Myopathy Muscle Skeletal Pathological Genetics (clinical) Aged Muscle Weakness business.industry Electromyography Incidence (epidemiology) Haplotype Middle Aged Founder Effect Pedigree 030104 developmental biology Phenotype Respiratory failure Mutation Hong Kong Female medicine.symptom business Founder effect Myopathies Structural Congenital |
| Zdroj: | Clinical geneticsREFERENCES. 97(5) |
| ISSN: | 1399-0004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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