Pre-natal Genetic tests
Jane and Joe Brown were going to have a baby, and as any other couple consulted their physician regarding the clinical tests that are recommended before trying to get pregnant. Among others, they conducted a set of genetic tests that were aimed at screening for a few mutations that are common in their population of origin (European Americans).
Luckily enough, the genetic screening results for the Browns were negative, meaning that neither of them is a carrier for the mutations tested. The pregnancy went well without any clinical complications or diagnoses, and so did the birth procedure.
Rare genetic disease
Unfortunately, the baby was diagnosed with a profound vision loss at birth, and further clinical signs pointed to a genetic disorder – Leber’s Congenital Amaurosis (LCA). The genetic team decided that since the diagnosis is very clear, a few genes that are known to be associated with LCA should be checked specifically using full sequencing. It means that each gene was sequenced individually, with prices ranging between a few hundreds to a few thousands US dollars per gene. All the sequencing results were negative – no mutation was found in the genes that went through sequencing. Now the Browns were in a dilemma. They could not be sure what was wrong with their daughter, therefore, could not get precise diagnosis and advice for treatment from their physicians. More importantly, the geneticist explained that LCA is usually inherited in a recessive way, which means that in any additional pregnancy, there is 25% probability that the baby will be born with this devastating disorder. The geneticist also stressed that there will be no way to diagnose the embryo (during the pregnancy), as the specific genetic mutation that was inherited from the parents was not identified.
The genetic team could go on with sequencing additional genes, increasing the costs without knowing where, in which gene, they should look. As an alternative, they could actually sequence all the genes in the genome at once using a new approach that was extremely expensive and inaccurate a few years ago but is reasonably priced and widely used since 2011 – whole exome sequencing.
In order to perform Exome Sequencing, blood samples were taken from the couple and their affected baby, and DNA was extracted and sent for sequencing. The resulting data is quite huge – approximately 20Gb of raw data. The genetic team used the services of Toldot Genetics to process and analyze these data with the aim of searching the entire individual genomes of the three family members for a single candidate mutation that causes LCA in this specific family.
The analysis at Toldot identified a deleterious mutation in the baby’s genome that was inherited from both parents, leaving the gene non-functional. The gene was well documented in the clinical literature to be associated with LCA, and actually, the mutation was already identified in the past in a few other families.
The geneticist could now tell the parents which gene should be examined in the next pregnancy to ensure that the baby will not be born with LCA.