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Somatic and germinal mosaicism in a Han Chinese family with laminopathies

European Journal of Human Genetics volume 31, pages 1073–1077 (2023)Cite this article

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Abstract

“Laminopathies” refers to a wide spectrum of myopathies caused by mutations in the LMNA gene. These myopathies include limb girdle muscular dystrophy type 1B (LGMD1B) and dilated cardiomyopathy 1 A (DCM1A), which are both autosomal dominant neurogenetic diseases. There have been few studies on mosaicism in laminopathies. Herein, a Han Chinese family with laminopathies was enrolled in our study. Genetic analysis revealed that the proband carried a novel splice site mutation, c. 1158-3 C > T, in the LMNA gene due to her mother having de novo somatic and gonadal mosaicism. Reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed reduced levels of LMNA mRNA in the proband, which were probably due to nonsense-mediated mRNA decay (NMD). Western blotting revealed reduced lamin A/C protein levels in the skeletal muscle tissue of the proband. In this family, the clinical phenotypes of the proband’s mother were normal, and the c. 1158-3 C > T splicing mutation was identified in the blood sample of the proband’s mother. Thus, the mutation could be easily considered to be nonpathogenic. Our study emphasizes the importance of mosaicism in the identification of pathogenic variants and genetic counseling.

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Fig. 1: Muscle pathology of the proband and her mother.
Fig. 2: Genetic analysis of the pedigree.
Fig. 3: Schematic diagram of parental and gonadal mosaicism in the proband’s mother.

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Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to express our sincere gratitude to all family members for their participation. This study was funded by National Natural Science Foundation of China (Grant No. 82271436) and Shandong Provincial Natural Science Foundation (Grant No. ZR2022MH190)

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Authors and Affiliations

  1. Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China

    Guangyu Wang, Ying Hou, Xiaoqing Lv, Chuanzhu Yan & Pengfei Lin

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  1. Guangyu Wang
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  2. Ying Hou
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  3. Xiaoqing Lv
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  4. Chuanzhu Yan
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  5. Pengfei Lin
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Contributions

GW, YH and XL collected the clinical characteristics and performed experiments. GW, YH and PL analyzed the data and wrote the manuscript. CY and PL revised the manuscript.

Corresponding author

Correspondence to Pengfei Lin.

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The authors declare no competing interests.

Ethical approval

The study was approved by the Ethics Committee of Qilu Hospital, Shandong University. All family members gave their written informed consent for muscle pathology and genetic analysis.

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Wang, G., Hou, Y., Lv, X. et al. Somatic and germinal mosaicism in a Han Chinese family with laminopathies. Eur J Hum Genet 31, 1073–1077 (2023). https://doi.org/10.1038/s41431-022-01266-9

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