Evidence of mild founder LMOD3 mutations causing nemaline myopathy 10 in Germany and Austria
| Autor: | Anna Schossig, Wolfgang H. Muss, Wolfgang M. Schmidt, Stephan Wenninger, Reginald E. Bittner, Simone Weiss, Benedikt Schoser, Sabine Rudnik-Schöneborn, Matthias Baumann, Ulrich A. Schatz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Muscle biopsy medicine.diagnostic_test business.industry Facial weakness medicine.disease Gastroenterology 03 medical and health sciences 030104 developmental biology Nemaline myopathy Internal medicine medicine Missense mutation Neurology (clinical) Allele medicine.symptom business Nemaline bodies Gene Founder effect |
| Zdroj: | Neurology. 91:e1690-e1694 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0000000000006428 |
| Popis: | ObjectiveTo expand the clinical and genetic spectrum of nemaline myopathy 10 by a series of Austrian and German patients with a milder disease course and missense mutations in LMOD3.MethodsWe characterized the clinical features and the genetic status of 4 unrelated adolescent or adult patients with nemaline myopathy.ResultsThe 4 patients showed a relatively mild disease course. They all have survived into adulthood, 3 of 4 have remained ambulatory, and all showed marked facial weakness. Muscle biopsy specimens gave evidence of nemaline bodies. All patients were unrelated but originated from Austria (Tyrol and Upper Austria) and Southern Germany (Bavaria). All patients carried the missense variant c.1648C>T, p.(Leu550Phe) in the LMOD3 gene, either on both alleles or in trans with another missense variant (c.1004A>G, p.Gln335Arg). Both variants were not reported previously.ConclusionsIn 2014, a severe form of congenital nemaline myopathy caused by disrupting mutations in LMOD3 was identified and denoted as NEM10. Unlike the previously reported patients, who had a severe clinical picture with a substantial risk of early death, our patients showed a relatively mild disease course. As the missense variant c.1648C>T is located further downstream compared to all previously published LMOD3 mutations, it might be associated with higher protein expression compared to the reported loss-of-function mutations. The apparent clusters of 2 mild mutations in Germany and Austria in 4 unrelated families may be explained by a founder effect. |
| Databáze: | OpenAIRE |
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