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Krenn, M.* ; Tomschik, M.* ; Wagner, M. ; Zulehner, G.* ; Weng, R.* ; Rath, J.* ; Klotz, S.* ; Gelpi, E.* ; Bsteh, G.* ; Keritam, O.* ; Colonna, I.* ; Paternostro, C.* ; Jäger, F.* ; Lindeck-Pozza, E.* ; Iglseder, S.* ; Grinzinger, S.* ; Schönfelder, M.* ; Hohenwarter, C.* ; Freimüller, M.* ; Embacher, N.* ; Wanschitz, J.* ; Topakian, R.* ; Töpf, A.* ; Straub, V.* ; Quasthoff, S.* ; Zimprich, F.* ; Löscher, W.N.* ; Cetin, H.*

Clinico-genetic spectrum of limb-girdle muscular weakness in Austria: A multi-centre cohort study.

Eur. J. Neurol. 29, 1815-1824 (2022)
Verlagsversion Forschungsdaten DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BACKGROUND: Hereditary myopathies with limb-girdle muscular weakness (LGW) are a genetically heterogeneous group of disorders, in which molecular diagnosis remains challenging. Our aim was to present a detailed clinical and genetic characterisation of a large cohort of patients with LGW. METHODS: This nationwide cohort study included patients with LGW suspected to be associated with hereditary myopathies. Parameters associated with specific genetic aetiologies were evaluated, and we further assessed how they predicted the detection of causative variants by genetic analyses. RESULTS: Molecular diagnoses were identified in 62.0% (75/121) of the cohort, with a higher proportion of patients diagnosed by next-generation sequencing (NGS) than by single gene testing (77.3% vs. 22.7% of solved cases). Median time from onset to genetic diagnosis was 8.9 years (IQR 3.7-19.9) and 17.8 years (IQR 7.9-27.8) for single gene testing and NGS, respectively. The most common diagnoses were myopathies associated with variants in CAPN3 (n = 9), FKRP (n = 9), ANO5 (n = 8), DYSF (n = 8) and SGCA (n = 5), together accounting for 32.2% of the cohort. Younger age at disease onset (p = 0.043), >10x elevated CK activity levels (p = 0.024) and myopathic electromyography findings (p = 0.007) were significantly associated with the detection of causative variants. CONCLUSIONS: Our findings suggest an earlier use of NGS in patients with LGW to avoid long diagnostic delays. We further present parameters predictive of a molecular diagnosis that may help to select patients for genetic analyses, especially in centres with limited access to sequencing.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Austria ; Limb-girdle Muscular Dystrophy ; Limb-girdle Muscular Weakness ; Myopathy ; Next-generation Sequencing; Pompe Disease; Dystrophies; Hyperckemia; Prevalence
ISSN (print) / ISBN 1351-5101
e-ISSN 1468-1331
Quellenangaben Band: 29, Heft: 6, Seiten: 1815-1824 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Begutachtungsstatus Peer reviewed
Förderungen Sanofi Genzyme