Ultrasound can detect certain malformations and anomalies in foetal development. In this case, we can look for a genetic cause using karyotyping[1] and chromosomal microarray analysis (CMA)[2]. In about 38% of cases, these analyses determine the cause of the disorder, but in “more than 60% of these pregnancies there is no diagnosis and nothing to guide genetic counselling”. Moreover, “in children with a presumed genetic pathology, sequencing the whole exome, i.e. every coding part of the genome, diagnoses a genetic cause in 25-35% of cases where karyotyping and CMA are negative”. This examination “can diagnose new inherited and ‘de novo’ variants, as well as variants previously identified in databases as probably pathogenic”.
In a study conducted at Columbia University in New York, whole exome sequencing was offered to parents after structural anomalies were discovered by ultrasound. In 10% of cases, this analysis diagnosed a genetic mutation associated with phenotype. In 20% of cases, whole exome sequencing “identified mutations that were potentially pathogenic but without sufficient evidence to confirm a causal link with the structural anomaly”. This discovery of “mutations of no known significance or unrelated to ultrasound results raises major ethical issues”. Whole exome sequencing during pregnancy is complex data analysis.
[1] which may show chromosome abnormalities (aneuploidies).
[2] which identifies losses or gains of small chromosome abnormalities.
Journal International de Médecine, Catherine Vicariot (26/02/2019)