Diagnosis put to the test

By | Science & Technology
Newborn receiving test at a hospital. Credit@SamuelKingJr

Breaking research has demonstrated for the first time that more precise DNA techniques may enable the identification of certain prenatal and newborn syndromes; 22q11.2 deletion syndrome in newborns, as well as Wilson’s in a fetus – with zero possibility of miscarriage associated with traditional prenatal techniques. The successes of these techniques were published in the Molecular Diagnostics.

22q11.2 deletion syndrome (22q11DS) is considered one of the most common chromosomal deletions responsible for birth defects. The deletion is observed on the long arm (q) of chromosome 22, on band 11.2. Each chromosome has a short arm (‘p’ for ‘petit’) and a long arm (‘q’ for ‘queue’), separated by a centromere. Each arm is divided further into regions called cytogenetic bands, counting from the middle of the chromosome to the outermost tip – the telomere. Therefore, the cytogenetic location of this particular deletion syndrome is towards the middle of chromosome 22 at q11.2. A small 3-Mb deletion in this region is most often the cause in individuals with 22q11DS.

There has been a strong drive to include 22q11DS in newborn screening panels to diagnose and treat infants from an early stage. This is because the condition is characterised by a number of different signs and symptoms affecting almost any part of the body, including heart abnormalities, learning difficulties and recurrent infections. Later in life, there is also an increased probability of developing mental conditions such as schizophrenia. However, even the best proposals until now have been too expensive and labour-intensive to be a viable solution.

Scientist conducting specialised testing. Credit@LabScienceCareer

Scientist conducting specialised testing. Credit@LabScienceCareer

For the first time, a team of scientists led by Flora Tassone at the University of California Davis Medical Center in Sacramento has shown how a technique called droplet digital polymerase chain reaction (ddPCR) can quantify DNA more precisely than ever. Using this method, the team was able to accurately identify 22q11DS in every sample tested. Moreover, this diagnosis may be performed economically at a cost of USD5-6 per reaction.

The second achievement in the field this week regards the molecular diagnosis of the rare hepatolenticular degeneration, more commonly known as Wilson’s. Wilson’s is the result of a mutation in the ATP7B gene. This is a recessive mutation, meaning two abnormal copies of the gene need to be inherited (one from each parent) to have an effect. The ATP7B gene is involved in constructing a protein that exports copper out of cells in the liver as well as other parts of the body – ‘copper-transporting ATPase 2’.

Copper is an essential ingredient to keep the human body ticking. Mutations in ATP7B prevent the transporter protein from functioning correctly, causing a build up of copper inside cells, affecting tissue and organs, particularly the liver and brain. If detected and treated early enough though, patients may lead perfectly healthy lives.

A research team at the Central South University, Hunan, China led by Lingyian Wu has developed a new, non-invasive technique named ‘circulating single-molecule amplification and resequencing technology’ (cSMART). cSMART has been proven to diagnose Wilson’s with an identical accuracy to traditional methods, just more safely. Up to now, prenatal diagnosis of Wilson’s is performed on fetql chorionic villus cells or by amniocentesis, however they may be invasive and hence carry a probability of miscarriage as well as other complications. This has been the case because safer and more traditional methods have been unable to detect Wilson’s so far. This is because the fetal gene product of interest is present at such minute levels in the mother’s blood that it is unable to be easily detected by traditional methods.

In theory, both of these techniques might be applicable to an entire spectrum of prenatal genetic disorders. This may revolutionise prenatal genetic diagnosis by providing a non-invasive way to test fetuses and newborns for rare conditions safely with the aim of ensuring a healthy start to life. Additionally, these techniques may even extend beyond prenatal diagnosis to early cancer diagnosis by accurately quantifying levels of tumour-specific DNA in the blood, as well as monitoring patients during therapy.

How might this potentially life-saving technique be productively applied to the diagnosis of other genetic conditions in the clinic?


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