Multiple deletions in mitochondrial DNA in a patient with progressive external ophthalmoplegia, leukoencephalopathy and hypogonadism.

Progressive external ophthalmoplegia (PEO) is one of a number of major types of mitochondrial disorders. Most sporadic PEO patients have a heteroplasmic large deletion of mitochondrial DNA (mtDNA) in the mitochondria in skeletal muscles. We herein analyzed mtDNA deletions using sub-cloning and Sanger sequencing of PCR products in a 31-year-old Japanese man with multiple symptoms, including PEO, muscle weakness, hearing loss, leukoencephalopathy and hypogonadism. A large number of multiple deletions was detected, as well as four kinds of deletion breakpoints identified in different locations, including m.3347_12322, m.5818_13964, m.5829_13964 and m.5837_13503.

Late-onset mental deterioration and fluctuating dystonia in a female patient with a truncating MECP2 mutation.

A 26-year-old woman with psychomotor developmental delay since late infancy showed rapid deterioration of her psychomotor abilities at the 11 years of age. She had gained the ability to verbally express herself and perform motor activities such as running and dancing in early childhood, but she lost the ability to verbally communicate and was unable to walk independently after this period. She also presented with dystonia in the right extremities, which markedly fluctuated with a periodicity of hours to months. Sleep disturbance and epileptic seizures also emerged during adolescence. Frontal lobe atrophy and hypoperfusion of the left cerebral hemisphere were noted on neuroimaging examinations. Analysis of the MECP2 gene revealed a late truncating mutation of c.1196_1200delCCACC (p.P399QfsX4) near the 3'-terminal of the coding region. The phenotype of this patient corresponds to the rare, unestablished variant of "late childhood deterioration" in MECP2-related disorders. For the first time, MECP2 mutation was confirmed to be the genetic basis of this condition.

The P86L common allele of CALHM1 does not influence risk for Alzheimer disease in Japanese cohorts.

A common P86L variant in CALHM1 was recently identified to increase susceptibility to Alzheimer disease (AD) in individuals of European-descent. To determine whether or not this association is also valid in a different ethnic population, we directly sequenced three nearby SNPs including P86L in more than 2,500 Japanese AD case-control samples. We found no association between CALHM1 P86L polymorphism and AD risk in Japanese individuals. We also found a small number of non-synonymous minor variants in both control and case populations, some of which are predicted to affect protein function, but are unlikely to increase this risk of AD in this population. We also determined that the P86L allele frequency is lower in non-Caucasian populations than in Caucasians. Our findings suggest that the CALHM1 P86L common variant may not influence AD risk in Japanese.

Superpositioning of deletions promotes growth of Escherichia coli with a reduced genome.

Escherichia coli has dispensable genome regions and eliminating them may improve cell use by reducing unnecessary metabolic pathways and complex regulatory networks. Although several strains with reduced genomes have already been constructed, there have been no reports of strains constructed with deletions assayed for influence on growth. To retain robust growth and fundamental metabolic pathways, the growth of each deletion strain and combination effects of deletions were checked using M9 minimal medium. Then a new strain, MGF-01, with a 1 Mb reduced genome was constructed by integrating deletions that did not affect growth. MGF-01 grew as well as the wild type in the exponential phase and continued growing after the wild type had entered the stationary phase. The final cell density of MGF-01 was 1.5 times higher than that of the wild-type strain. Using MGF-01 as a production host, a 2.4-fold increase in l-threonine production was achieved.