Prenatal diagnosis is sometimes complicated by the results of high-throughput sequencing.

A team from Dijon reports on a complex situation involving a consanguineous couple whose foetus carried adevelopmental anomaly known as cystic hygroma:

• a whole exome trio (WES-Trio) study was carried out prenatally to determine the origin,
  
• a homozygous truncating variant of the ASCC1 gene was identified, known to give a very rare form of spinal muscular atrophy accompanied by fractures,
  
• the same analysis identified a variant, also truncating, in another gene, CSPP1, usually responsible for Joubert syndrome,
  
• it was only during genetic counselling for the next pregnancy that the CSPP1 variant was definitively ruled out as non-causal.
  

This observation illustrates the complexity of interpreting high-throughput sequencing data in the prenatal period, during which it is often difficult to accurately predict the future phenotype.

 

Early prenatal diagnosis of causative homozygous variants in ASCC1 in a fetus with cystic hygroma and additional homozygous variants of unknown significance associated with a neurological phenotype not visible in early gestation: Dual diagnosis or not? Favier M, Delanne J, Gorincour G et al. Prenat Diagn. 2024 Mars.