Mutations in CERS3 Gene Underlies a Case of Autosomal Recessive Congenital Ichthyosis / 罕见病研究

Autosomal recessive congenital ichthyosis caused by CERS3 mutations is extremely rare in clinical practice. We recently identified a family of autosomal recessive congenital ichthyosis and performed multigene exome sequencing for hereditary skin diseases to identify causative genes. Mutation analysis revealed compound heterozygous mutations of c.746A>G(from the mother) and exon12 deletion(from the father)in CERS3 were detected in the proband, which were verified by Sanger sequencing and co-segregated with the ichthyosis phenotype in the proband and her parents. These mutations were both reported for the first time. For the treatment, the proband received an oral acitretin capsules of 20 mg once daily. After 3-month follow up, the patient's lesion improved significantly.

Large Deletion in KCNQ1 Identified in a Family with Jervell and Lange-Nielsen Syndrome

Long QT syndrome (LQTS) is a genetically heterogeneous disorder associated with sequence variations in more than 10 genes; in some cases, it is caused by large deletions or duplications among the main, known LQTS-associated genes. Here, we describe a 14-month-old Korean boy with congenital hearing loss and prolonged QT interval whose condition was clinically diagnosed as Jervell and Lange-Nielsen syndrome (JLNS), a recessive form of LQTS. Genetic analyses using sequence analysis and multiplex ligation-dependent probe amplification (MLPA) assay revealed a large deletion spanning exons 7-10 as well as a frameshift mutation (c.1893dup; p.Arg632Glnfs*20). To our knowledge, this is the first report of a large deletion in KCNQ1 identified in JLNS patients. This case indicates that a method such as MLPA, which can identify large deletions or duplications needs to be considered in addition to sequence analysis to diagnose JLNS.

Pattern of Exon Deletions of Dystrophin Gene in Korean Patients with Duchenne Muscular Dystrophy

OBJECTIVE: To investigate the pattern of exon deletions in Korean patients with Duchenne muscular dystrophy (DMD), and to find the correlation of the exon-deletion with clinical symptoms or laboratory findings. METHOD: Genomic DNA of the nine children with DMD were analyzed by the sets of multiplex PCR and one singlet PCR in total of fifteen primers of the dystrophin gene. The primers were made from the promotor, and the exons 3, 4, 6, 8, 12, 13, 43, 44, 47, 48, 50, 51, 52 and 60 of the dystrophin gene, respectively. RESULTS: Eight out of nine patients revealed exon deletions. The exon 3 was most commonly deleted (6 patients), and exon 48, 50 and 60 were second most common (2 patients). The exons 4, 6, 13, 44, 47 and 52 were not deleted in all patients. CONCLUSION: We found that the exons 3, 48, 50 and 60 are frequently deleted in Korean patients with DMD. The pattern of deletion was not correlate with clinical symptoms or laboratory findings.

Deletion of Exon in the Dystrophin Gene in a Case of Becker Muscular Dystrophy with Cardiac Involvement

Progressive muscular dystrophy (PMD) is an X-linked recessive primary muscular disease characterized by progressive muscular weakness. It causes gait disturbance and complications such as pneumonia, heart failure, and aspiration, so lead to death. Becker muscular dystrophy (BMD) is a milder type of PMD, of which incidence is 5 cases per 100,000 populations. It begins later and evolves more slowly than Duchenne muscular dystrophy (DMD). In PMD patients without heart failure symptom, there may be ECG abnormality or ventricular dilatation, impaired ventricular function which is consistent with dilated cardiomyopathy, especially in DMD. In BMD, heart failure is rare but ECG or echocardiographic abnormality is often found. With the advance of molecular genetics, mutations of the dystrophin gene is proved to be related to the pathogenesis of PMD and dilated cardiomyopathy. We confirmed the deletion of exon 43-51 in the dystrophin gene a case of BMD with asymptomatic dilated cardiomyopathy, diagnosed by echocardiography.

Deletion of Exon in the Dystrophin Gene in a Case of Becker Muscular Dystrophy with Cardiac Involvement

Progressive muscular dystrophy (PMD) is an X-linked recessive primary muscular disease characterized by progressive muscular weakness. It causes gait disturbance and complications such as pneumonia, heart failure, and aspiration, so lead to death. Becker muscular dystrophy (BMD) is a milder type of PMD, of which incidence is 5 cases per 100,000 populations. It begins later and evolves more slowly than Duchenne muscular dystrophy (DMD). In PMD patients without heart failure symptom, there may be ECG abnormality or ventricular dilatation, impaired ventricular function which is consistent with dilated cardiomyopathy, especially in DMD. In BMD, heart failure is rare but ECG or echocardiographic abnormality is often found. With the advance of molecular genetics, mutations of the dystrophin gene is proved to be related to the pathogenesis of PMD and dilated cardiomyopathy. We confirmed the deletion of exon 43-51 in the dystrophin gene a case of BMD with asymptomatic dilated cardiomyopathy, diagnosed by echocardiography.