Paediatrics: Molecular genetic analysis

Molecular genetic analysis

The human genome contains 73,000,000,000 DNA base pairs and 725,000 genes. In genetic disorders, the pathology may range from a whole extra chromosome, e.g. Down syndrome, to a single DNA base pair alteration, e.g. achondroplasia. Molecular genetic tests are highly specific tests that only reveal information about one very specific gene analysis, generally selected because of a strong clinical diagnosis, e.g. achondroplasia.

•   If there is a commonly occurring mutation, analysis is simple and comparatively inexpensive, e.g. cystic fibrosis and the CF29 kit tests for the 29 most common mutations in the Caucasian population, and achondroplasia in which two common mutations, G1138A and G1138C in the FGFR3 gene, account for 798% of mutations in children with achondroplasia).

•   If the mutation in a family is known, analysis is usually straightforward and takes 72–6 weeks for most tests. Such tests, based on information obtained from other family members, should involve a clinical geneticist.

•   If the mutation is unknown, an entire gene may have to be sequenced. Genetic testing in this situation can be laborious, expensive (often 7£1000), and only a small proportion may be available as diagnostic tests. In the UK, reporting times are being reduced for these tests and now routinely take about 6–8wks, even for a very large challenging gene, e.g. FBN1 in Marfan syndrome and TSC1 and TSC2 in tuberous sclerosis. Consult a clinical geneticist about whether genetic testing is appropriate in  these circumstances.