Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center.

INTRODUCTION: Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene. METHODS: We analyzed the dystrophin gene in 507 Korean DMD/BMD patients by multiple ligation-dependent probe amplification and direct sequencing. RESULTS: Overall, 117 different deletions, 48 duplications, and 90 pathogenic sequence variations, including 30 novel variations, were identified. Deletions and duplications accounted for 65.4% and 13.3% of Korean dystrophinopathy, respectively, suggesting that the incidence of large rearrangements in dystrophin is similar among different ethnic groups. We also detected sequence variations in >100 probands. The small variations were dispersed across the whole gene, and 12.3% were nonsense mutations. CONCLUSIONS: Precise genetic characterization in patients with DMD/BMD is timely and important for implementing nationwide registration systems and future molecular therapeutic trials in Korea and globally. Muscle Nerve 55: 727-734, 2017.

Significance of local international sensitivity index systems for monitoring warfarin and liver function.

OBJECTIVES: Use of a local calibrator has been recommended for standardization of the international normalized ratio (INR) and international sensitivity index (ISI). We investigated the performance of two commercial local calibrators for warfarin monitoring and determined the significance of liver-specific INR. METHODS: ISI values were determined using the World Health Organization (WHO) method and two commercial local calibrators. Liver-specific ISI was determined using plasma samples from patients with liver cirrhosis and normal controls. RESULTS: In warfarin monitoring, the two local ISIs determined by the two local calibrators showed better consistency than uncorrected ISI, although they were inferior to the ISIs calibrated using the WHO method. Alternative calibration using calibration plasma from patients with liver cirrhosis instead of warfarinized plasma reduced the INR variability. CONCLUSIONS: Local ISI determined by a commercial local calibrator improved INR standardization among thromboplastins. The alternative ISI calibration using liver-specific calibration plasma is expected to reduce INR variability for the evaluation of liver function.

A case report of Fanconi anemia diagnosed by genetic testing followed by prenatal diagnosis.

Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.