Abstract
Prenatal diagnoses are probably the most high-risk tests undertaken by genetics laboratories. Misdiagnosis potentially results in the birth of a child with a painful and distressing condition or, conversely, the termination of a pregnancy carrying a healthy fetus. Prenatal diagnoses are carried out for a wide range of genetic conditions and a diverse range of methods are required. In this one volume the editors have brought together detailed descriptions of an astonishing array of genetic procedures available to the molecular genetic diagnostic laboratory.
The first part of the book focuses on more traditional approaches to prenatal molecular genetic diagnosis based on obtaining fetal tissue samples such as chorionic villus biopsies or amniocytes by invasive methods. The majority of analytical methods described are standard techniques; however, new methods still in evaluation are also included.
The second part of the book explores prenatal diagnosis using non-invasive sampling methods to obtain fetal material for testing: a method referred to as NIPD (non-invasive prenatal diagnosis). These methods predominantly involve sampling maternal plasma to obtain cell-free fetal DNA, RNA, proteins or metabolites. Methods for testing cell-free fetal DNA have been in development since around 2001 and have been in limited routine practice since around 2005. One important application is the determination of fetal rhesus D status in fetuses of rhesus-negative mothers to prevent the risk of maternal alloimmunization to the RhD antigen and eliminate the major cause of haemolytic disease of the fetus and newborn. A second important application of NIPD is for the determination of fetal sex in pregnancies at risk of a sex-limited or sex-linked genetic disorder.
The editors have elicited contributions from an international cast of expert authors. The contributions span a wide scope of genetic disorders ranging from the relatively common aneuploidies where screening approaches are required to rare genetic diseases including inherited metabolic disorders. Most chapters have succinct introductions that clearly set out the purpose of the prenatal diagnostic method under discussion and in the case of the more recent innovations the rationale for moving away from traditional methods. It was pleasing to see that many authors were comfortable explaining the merits of the traditional methods of analysis, be it enzyme assay or karyotyping, and the circumstances in which such approaches are more appropriate.
One downside of the internationally recognized team of contributors is the unusual use of English in some chapters which, in my opinion, ought to have been corrected at the copy-editing stage.
A number of chapters describe methods in evaluation, which is an inspiring aspect of this book but I felt in some instances the boundaries between routine practice and development were not always clear. The genetic testing community is acutely aware of the disappointments patients experience when the latest tests they find described on the Internet are not actual clinical reality. Audits of the reliability of the various methods would give the non-expert reader an opportunity to discern the tried and trusted methods from the recent innovations not yet in routine practice.
I was disappointed by the paucity of figures and illustrations of data. These are such helpful tools for non-specialist readers of technical material. Nonetheless, protocols for the methods described appear to provide sufficient detail for the technically competent to replicate the procedures. The troubleshooting sections of each chapter are limited to technical notes and might have benefitted from being given a more systematic structure.
In summary, this is a valuable text for individuals and laboratories that carry out prenatal diagnoses; whether or not they currently use molecular biology techniques, these will inevitably impinge on their practice in the near future. This book neatly brings together a breadth of technical, clinical and academic experience in one volume that provides a helpful resource for all professional groups involved in prenatal testing including obstetrics, genetics and public health screening laboratories.