~]OOK ~k~EVIEWS

regulation, too often seem to see the eukaryotic genetic material with prokaryotic vision. For those of us who teach the structure and func- tion of chromatin - and Cbromatin is a testament to the breadth, diver- sity and importance of the subject today - the book will prove invalu- able. It is unfortunate that such a

seminal text will reach only a restricted student audience because, at such a high price, few will be able to afford their own copy.

ROGER PAI"I~ AND JIM ALLAN

Division of Biomolecular Sciences, King's College, UniversiO, of London, London, UK.

Cystic Fibrosis edited by Peter Goodfellow, Oxford University

Press, 1989. £15.00 (ix + 96 pages) ISBN 0 19 261835 0

The Fragile X Syndrome edited by Kay E. Davies, Oxford University

Press, 1989. £15.00 (v + 138 pages) ISBN 0 19 261836 9

Cystic fibrosis (CF) is the common- est genetic disorder in Western societies (but very rare in, for example, the Orient), affecting about 1 in 2000 newborns with roughly 1 in 20 individuals being carriers of the autosomal recessive gene. But there is no cure for this serious condition, and the basic defect was until recently not known. The aim of this little book, in the words of the editor, is 'to stimulate research at the interface between the medtcal and scientific professions' in the belief that it will generate insights that could be pro- ductive. For the scientist interested in the disease there are reviews of the clinical features (Jackson) and management (Dodge), and for the clinician there are reviews of epithelial ion transport where the basic defect no doubt resides (Cuthbert), possible approaches to identifying the molecular basis of CF (Van Heyningen and Porteous), and prenatal diagnosis using linked probes and microvillar enzymes (Brock).

However, these last two chap- ters have been somewhat overtak- en by events. Since the book went to press the defective gene (about 250 kb in size) has been identified by collaborating groups in Toronto (excellently reviewed by the editor

himself in Nature, 14 September 1989). These studies indicate that about 70% of gene mutations are due to a specific deletion of a codon for phenylalanine (at position 508 of the gene product), the remainder of the patients having different mutations. The ability to detect specific mutations in the CF gene at the DNA level (using oligoprobes for example) opens up the possibilities of precise diagnosis both postnatally and prenatally, as well as popu- lation screening for heterozygous carriers. Population geneticists will also welcome these developments as providing a specific tool for investigating haplotype evolution and dispersion within different populations, and perhaps the knotty problem of heterozygote advantage.

The putative gene product has been termed CF transmembrane regulator (CFTR) and elucidation of its function will lead to a better understanding of pathogenesis and hopefully to a rational therapy. It is to be hoped that the editor will be encouraged to produce a new edition of this excellent text when answers to some of these problems become clearer- hopefully in the not too distant future.

The Fragile X Syndrome, like Cystic Fibrosis part of the Molecular Medicine series, sum- marizes in five detailed reviews our current knowledge of the fragile X syndrome. The clinical features (Fryns) are characterized by the triad of mental retardation, long face with large ears, and large testes, and about a third of female carriers are also mentally retarded. Life expectancy is normal. Intriguing observations, which so far have not been explained, include the high incidence of twin- ning among the offspring of female carriers and the fact that normal males in a family may occasionally

T1G JANUARY 1990 VOL. 6 XO. 1

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transmit the condition to their descendants. There now seems little doubt that this is a relatively common condition and various epi- demiologicai studies (Webb) indi- cate that it occurs in the general population in roughly 1 in 1000 males and in 1 in 2000 females, and in institutions for the mentally handicapped in 1 in 10 males. It is therefore second only to Down syndrome as a specific cause of mental handicap. Cognitive and behavioural studies (Hagerman) have revealed a significant decline in intelligence throughout child- hood and a proportion of cases exhibit iwpemctivity and even autism.

The cytological observation on which the diagnosis is made (a nonstaining gap at Xq27.3) can be induced in culture by a folate- deficient medium or the addition of methotrexate (a folate antagonist) or fluorodeoxyuridine (an inhibitor of thimidylate synthetase). The cytogenetics of the disorder (Tommerup) are reviewed in detail, and it is clear that the fragile site is not cell specific nor is there any evidence that it occurs in vivo. The fact that it can be difficult to demonstrate in cultured amniotic fluid cells or chorionic villus cells has been a stimulus to develop linked DNA markers for prenatal diagnosis (and carrier detection). A review of DNA studies (Brown) indicates that a number of m:trkers are candidates, though none is very close to the fragile site, and at least one (factor IX) seems to be linked in some families but not others. However, by a combination of cytogenetic and DNA studies, coupled to careful family and clini- cal studies it is now possible to offer reliable counselling and pre- natal diagnosis to many of the more extensive affected families. The race is now on to isolate and characterize the fragile X DNA sequence.

This well documented and authoritative text can be highly recommended to anyone interested in the fragile X syndrome, one of the most intriguing of all genetic diseases.

AL~E~mv

Medical School. Teviot Place. Edinburgh EH8 9AG. UK.