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Objective:The purpose of this work was to obtain the phenotypes and detect potential mutations in three Chinese patients with Marfan syndrome (MFS) or incomplete MFS phenotypes.Methods:Three unrelated patients with a definite or suspected clinical diagnosis of MFS and their family members were recruited for research. Genomic DNA was extracted from peripheral blood of these patients and their family members. All the exons were sequenced by next-generation sequencing and the variants were further validated by Sanger sequencing. The functional consequences of the mutations were analyzed with various genomic resources and bioinformatics tools.Results:Three FBN1mutations were identified in the three patients, including one novel mutation (2125G > A) and two previously reported mutations (4786C > T and 6325C > T). It was interesting to note that the parents of these patients were normal as assessed by clinical features or genetic testing, but all these mutations were detected in their offspring, except for the variant 6325C > T. We also found that a few young members of the family of probands (proband 1 and proband 2) have exhibited no manifestations of MFS so far, although they carry the same disease-causing mutation.Conclusions:We found three FBN1mutations in three unrelated Chinese families with MFS by genome sequencing, and the relationship between genotypes and phenotypes in MFS patients needs further exploration.

Familial dilated cardiomyopathy (DCM) is associated with numerous genes, especially those of the sarcomere family. The titin gene (TTN) consists of 365 exons and encodes the largest sarcomere protein (titin) in our bodies. Titin is associated with many diseases, such as hypertrophic cardiomyopathy and DCM. Here we screened three Chinese families affected by DCM, and found that each harbors a stop-gain or splice site mutation in TTN(c.G20137T,c. G52522T,c.44610-2A>C). Assessment of the probands by electrocardiogram, B-mode echocardiography, and cardiac magnetic resonance imaging revealed impaired cardiac function, arrhythmia, or abnormal cardiac structure. In conclusion, using whole exome sequencing, we found three unreported TTNmutations associated with DCM. This has expanded the TTNmutation spectrum of Chinese DCM patients, especially in Henan, the most populous province. These data provide new genetic targets for the diagnosis and treatment of DCM, and will increase our understanding of the relationship between TTNmutation and DCM clinical symptoms.

Long QT syndrome (LQTS), which is caused by an ion channel‐related gene mutation, is a malignant heart disease with a clinical course of a high incidence of ventricular fibrillation and sudden cardiac death in the young. Mutations in KCNH2 (which encodes potassium voltage-gated channel subfamily H member 2) are responsible for LQTS in many patients. Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing. The c.916dupA mutation in JUP (which encodes junction plakoglobin) is also discovered. Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy. The double mutation in the proband may help explain his severe clinical manifestations, such as sudden cardiac death at an early age. Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line, while the mutation in JUP came from his maternal line. The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.