Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan (incidence is 0.7-1.2 per 10,000 births), is characterized by congenital muscular dystrophy associated with brain malformation (micropolygria) due to a defect in the migration of neurons. We previously mapped the FCMD gene to a region of less than 100 kilobases which included the marker locus D9S2107 on chromosome 9q31. We have also described a haplotype that is shared by more than 80% of FCMD chromosomes, indicating that most chromosomes bearing the FCMD mutation could be derived from a single ancestor. Here we report that there is a retrotransposal insertion of tandemly repeated sequences within this candidate-gene interval in all FCMD chromosomes carrying the founder haplotype (87%). The inserted sequence is about 3 kilobases long and is located in the 3' untranslated region of a gene encoding a new 461-amino-acid protein. This gene is expressed in various tissues in normal individuals, but not in FCMD patients who carry the insertion. Two independent point mutations confirm that mutation of this gene is responsible for FCMD. The predicted protein, which we term fukutin, contains an amino-terminal signal sequence, which together with results from transfection experiments suggests that fukutin is a secreted protein. To our knowledge, FCMD is the first human disease to be caused by an ancient retrotransposal integration.

SummaryHigh-purity cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are promising for drug development and myocardial regeneration. However, most hiPSC-derived CMs morphologically and functionally resemble immature rather than adult CMs, which could hamper their application. Here, we obtained high-quality cardiac tissue-like constructs (CTLCs) by cultivating hiPSC-CMs on low-thickness aligned nanofibers made of biodegradable poly(D,L-lactic-co-glycolic acid) polymer. We show that multilayered and elongated CMs could be organized at high density along aligned nanofibers in a simple one-step seeding process, resulting in upregulated cardiac biomarkers and enhanced cardiac functions. When used for drug assessment, CTLCs were much more robust than the 2D conventional control. We also demonstrated the potential of CTLCs for modeling engraftments in vitro and treating myocardial infarction in vivo. Thus, we established a handy framework for cardiac tissue engineering, which holds high potential for pharmaceutical and clinical applications.

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome, and muscle-eye-brain disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. FCMD is frequent in Japan, but no FCMD patient with confirmed fukutin gene mutations has been identified in a non-Japanese population. Here, we describe a Turkish CMD patient with severe brain and eye anomalies. Sequence analysis of the patient's DNA identified a homozygous 1bp insertion mutation in exon 5 of the fukutin gene. To our knowledge, this is the first case worldwide in which a fukutin mutation has been found outside the Japanese population. This report emphasizes the importance of considering fukutin mutations for diagnostic purposes outside of Japan.

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Campylobacter jejuni was isolated from stool cultures from 14 (30%) of 46 patients with Guillain-Barré syndrome and from 6 (1.2%) of 503 healthy persons, and the difference was highly significant (p < 0.0001). In addition, serological evidence of recent C. jejuni infection was found in 5 of 29 patients with negative stool cultures. Therefore, 41% of patients were associated with C. jejuni infection. Ten of 12 (83%) isolates from patients with Guillain-Barré syndrome belonged to Penner serogroup 19, which is a rare serogroup in sporadic patients with C. jejuni enteritis. In the lectin typing study, all serogroup 19 strains from patients with Guillain-Barré syndrome were shown to contain terminal beta-N-acetylglucosamine residues on their cell surface, but serogroup 19 strains from patients with enteritis were not.