Friedreich ataxia is caused by an intronic gaa triplet repeat expansion

Biomed

& Pharmacorher

1997;51:44-5 0 Elsevier. Paris

Notes

Acute hepatitis

by parvovirus

B19

Human parvovirus B19 (B19) infection shows a broad spectrum of clinical manifestations such as erythema infectiosum in children, aplastic crisis in patients with haemolytic anaemia, chronic bone marrow failure in immunocompromised hosts and hydrops fetalis by intrauterine infection. We recently had the opportunities to examine samples from children with erythema infectiosum who had liver dysfunction. The role of B19 in pathogenesis of hepatic involvement was investigated retrospectively using the polymerase chain reaction assay of stored serum samples from 773 patients admitted to our hospital. Fifteen patients admitted to our hospital from January 1991 to June 1992 were B19 DNA positive, of whom four had acute hepatitis of unknown origin. These four patients were aged between 7 months and 5 years. Of the seven patients, infection with hepatitis A, B, or C viruses or Epstein-Barr virus was ruled out in six by virological examinations. Epidemiological evidence suggests that B19 can be the cause of acute hepatitis. Y Yoto (1) Sapporo Medical University, School of Medicine Sapporo 060. Japan

(1) Lancer

1996;347:868-9.

Friedreich ataxia is caused by an intronic triplet repeat expansion

GAA

Friedreich ataxia (FRDA) is an autosomal recessive, degenerative disease of childhood and early adulthood, that involves the central and peripheral nervous system and the heart. We identified a gene, X25, in the critical region for the FRDA locus on chromosome 9ql3. X25 encodes a protein, frataxin, whose mRNA is found at higher levels in tissues that undergo atrophy in FRDA, particularly spinal cord and heart. The X25 transcript undergoes alternative splicing, and the major frataxin isoform, 210 amino acid long, has homologues in distant species such as C elegans and yeast. No similarity with proteins of known function was found. A few

FRDA patients were shown to have point mutations in X25, but the vast majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron. Normal chromosomes have 7-22 GAA triplets, while FRDA chromosomes usually contain 700800 triplets, although occasionalsmaller (200) and larger (> 900) alleles have been observed. X25 mRNA was significantly reduced in FRDA patients when compared to normal controls, indicating that the intronic GAA expansion leads to disease by suppressing X25 expression. M Pandolfo (2) Baylor College of Medicine Houston, TX 77030, USA

(2) Science

1996;271: 1423-6.

Stroke and plaque in the aortic arch In a recent case control study, Amarenco et al noted an association between stroke and plaque in the aortic arch (N Engl J Med 1994;33 1:1474), confirming what they previously found in an autopsy study (N Engl J Med 1992;326:21). Now the same group presents a prospective study of this problem among 331 patients aged 60 or older hospitalized with acute brain infarction. Each patient underwent brain imaging, carotid and vertebral artery ultrasound, and transesophageal echocardiopgraphy (TEE), BY TEE, aortic arch wall thickness was at least 4 mm in 14% of patients, 1.0-3.9 mm in 43% and less than 1 mm in 43%. The first two groups were considered to have atherosclerotic plaque. During an average follow-up of 2.4 years, the incidence of recurrent brain infarction rose progressively, from 2.8 per 100 person-years among those with no plaque to 11.9 among patients with 4-mm plaque. The latter group also had a four-fold increase in the risk of any vascular event. Thick plaques remained a significant predictor of stroke and other vascular events after adjustment for carotid stenosis, atrial fibrilation, smoking, and other factors. Aortic arch plaque is probably both a source of cerebral emboli and a marker for generalized atherosclerotic