A Novel Mutation Of The EMD Gene In A Family With Cardiac Conduction Abnormalities And A High Incidence Of Sudden Cardiac Death

Demiao Kong,1,2,* Yi Zhan,3,* Canzhao Liu,4 Yerong Hu,1 Yangzhao Zhou,1,4 Jiawen Luo,1 Lu Gu,1 Xinmin Zhou,1 Zhiwei Zhang1,4 1Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; 2Department of Thoracic Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou 550002, China; 3Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; 4Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA*These authors contributed equally to this workCorrespondence: Zhiwei ZhangDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Changsha, Hunan 410011, People’s Republic of ChinaTel +86 13787083210 Email somebody_zhang@csu.edu.cnBackground: Emery-Dreifuss muscular dystrophy, caused by mutations in genes such as emerin (EMD) or lamin A/C (LMNA), is a disorder affecting the joints, muscles, and heart, with a wide spectrum of patient phenotypes including muscle wasting and cardiac conduction defects.Methods and results: Here we report a multi-generation family from the Hunan Province of China. Affected family members displayed an uncommon clinical presentation of serious cardiac conduction abnormalities at an early age and a high incidence of sudden cardiac death along with mild skeletal muscular atrophy and joint contracture. Clinical analysis of affected members provided evidence of X-linked recessive inheritance. Consequently, using Sanger sequencing of X chromosome exomes, we identified a novel duplication mutation (c.405dup/p.Asp136X) in the EMD gene as the cause for the disease in this family. This variant is a novel mutation that has not been previously reported in Pubmed, Clinvar or other cases reported in the Human Gene Mutation Database.Conclusion: Our finding expands the mutation spectrum of Emery-Dreifuss muscular dystrop