Medical Genetics Today

Author: D. Donnai
Submitted: Tuesday 14th of September 2010 04:45:00 PM
Submitted by: egf
Educational levels: expert, qc1, qc2, qc3



Medical Genetics today is built on a distinguished history of clinical, scientific and technological contributions. Over the 55 years since the discovery of the structure of DNA and the ~ 40 years since the introduction of chromosome analysis for diagnostic purposes an increasing range of services has been available to benefit patients with genetic disorders and their families. Careful clinical observation is at the heart of medical genetic practice. Many important observations were made before the technology to explore them further existed (see review by Harper 2005). The new technologies enabling targeted capture and massively parallel sequencing of individual genomes/exomes have resulted in major discoveries on small clinically well characterised patients (Ng et al 2009, Ng et al 2010, Hoischen et 2010). Other examples demonstrating the importance of clinical studies are those that predated the recognition of the mutational mechanism in three relatively common genetic disorders. Myotonic dystrophy was long known to manifest the phenomenon called anticipation, where the offspring of mild or moderately affected women tended to be much more severely affected. Similarly in Huntington’s Disease, children of classically affected fathers sometimes had onset in childhood, and in Fragile X families there were apparently unaffected transmitting males in early generations and the risk of an affected child seemed to increase down the generations. Eventually it turned out that all of these disorders shared a novel mutational mechanism, namely unstable trinucleotide repeats within the affected gene that tend to increase in number between generations. (La Spada AR, Taylor JP 2010). Similarly the concept of syndrome families (now known to closely match development pathways) was based largely on clinical observation (Spranger 1985, see review by Brunner and van Driel 2004). Some may argue that Medical Genetics as a clinical/laboratory specialty is not needed and that systems specialists and pathology laboratories can provide all that is needed. However I would argue that there are skills not available in other specialist clinics that we bring which considerably enhance patient care. We offer services for patients and families, for all age groups, for all body systems and over generations and time. We have knowledge of rare disorders – diagnosis, natural history and complications. We can offer or advise on screening, monitoring, prevention of complications (anticipatory care) and therapies. We offer genetic counselling to affected and apparently healthy people and are a major source of information to families, support groups, other professionals in health and social and in education. Much research in medical genetics has been to uncover the mechanisms underlying rare monogenic disorders. Collaboration between colleagues has enabled the collection of unique patient cohorts and families. Traditional mapping approaches for identifying genes have been used for many disorders but study of key patients with a translocation, deletion or an unusual clinical feature have also led to identification of genes involved in the pathogenesis of a number of syndromes. As these genes have been identified new developmental pathways have been elucidated and many disorders with overlapping clinical features shown to be due to functionally related genes. There has been great progress in disorders due to mutation of genes in the RAS/MAPK pathway (Denayer et al. 2008). Medical Genetics as a clinical specialty is constantly changing. The last 15 years has seen a massive increase in referrals of conditions generally regarded as common complex disorders such as breast and bowel cancer and some cardiac diseases. The first challenge has been to separate out those families with a ‘monogenic subset’ of the disease which are the only group which our current services can help. Meanwhile large scale research efforts such as the Wellcome Trust Case Control Consortium ( have been making progress looking for genetic variations – generally of small effect – which contribute to the pathogenesis of common disorders. Genetics is set to influence greatly the practice of medicine in the future. The role of clinicians and scientists in Medical Genetics departments are likely to change. Certainly we will be called upon to educate our colleagues in other specialties and engage more with patient groups and the public. However our clinical roles are also likely to change; we may for example have treatments for some of the conditions we already see, we may be involved in disease stratification as part of multidisciplinary teams involved in clinical trials and genetic laboratories may have a role in pharmacogenetic testing. Maybe the time has come to change the name of our specialty from Medical Genetics to Genetic Medicine. Brunner HG, van Driel MA. From syndrome families to functional genomics. Nat Rev Genet. 2004;5:545-51 Denayer E, de Ravel T, Legius E. Clinical and molecular aspects of RAS related disorders. J Med Genet 45. 695-703. 2008 Harper PS. Julia Bell and the Treasury of Human Inheritance. Hum Genet 2005;116:422-32 Hoischen A et al. De novo mutations of SETBP1 Cause Schinzel Gideon syndrome. Nature Genetics. Advance on line publication April 2010 La Spada AR, Taylor JP. Repeat expansion disease: progress and puzzles in disease pathogenesis. Nature Genetics Reviews 11. 247-258.2010 Ng SB et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461.272-276. 2009 Ng SB et al. exome sequencing identifies the cause of a mendelian disorder. Nature Genetics 42. 30-36. 2010 Spranger J. Pattern recognition in bone dysplasias. Prog Clin Biol Res 1985; 200:315-42


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D. Donnai. Medical Genetics Today. EUROGENE portal. September 2010. online:

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