Abstract
The molecular basis of autosomal dominant spinal muscular atrophy (AD-SMA) is largely unknown. Because the phenotypic spectrum of diseases caused by LMNA mutations is extremely broad and includes myopathies, neuropathies, and cardiomyopathies designated as class 1 laminopathies, we sequenced the LMNA gene in index patients with the clinical picture of proximal SMA, who had a family history suggestive of autosomal dominant inheritance. Among the 19 families investigated, two showed pathogenic mutations of the LMNA gene, resulting in the diagnosis of a class 1 laminopathy in about 10% of our series. We found one novel truncating mutation (c.1477C > T, Q493X) and one previously described missense mutation (c.1130G > T, R377H) in the LMNA gene of two unrelated patients with adult-onset proximal SMA followed by cardiac involvement 14 and 22 years after the onset of weakness. The pedigrees of both families revealed a high frequency of cardiac abnormalities or sudden deaths. Our findings extend the spectrum of laminopathies and are of relevance for genetic counseling and clinical care of families presenting with adult-onset proximal SMA. Particularly, if neurogenic atrophy is combined with a cardiac disease in a family, this should prompt LMNA mutation analysis.
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Acknowledgments
The authors wish to thank the affected families for their participation in the study. MW was supported by a grant of the BMBF 01GM0302, MD-NET.
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Rudnik-Schöneborn, S., Botzenhart, E., Eggermann, T. et al. Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy. Neurogenetics 8, 137–142 (2007). https://doi.org/10.1007/s10048-006-0070-0
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DOI: https://doi.org/10.1007/s10048-006-0070-0