Prenatal diagnosis of skeletal dysplasias using a targeted skeletal gene panel

This study aimed to perform an accurate and precise diagnosis for fetuses with suspected skeletal anomalies based on an incomplete and limited ultrasound phenotype.

Proband-only targeted skeletal gene panel sequencing was performed on 12 families who had fetuses with suspected skeletal anomalies based on ultrasound evaluations at a mean gestational age of 24 weeks and 3 days. The fetuses all had normal standard genetic testing yield (karyotyping and microarray).

In 10 of 12 fetuses, panel sequencing provided a diagnosis or possible diagnosis with identification of variants in the following genes: FGFR3, COL1A2, IHH, COL2A1, and DYNC2H1. Two cases revealed novel variants in COL2A1 and DYNC2H1.

Our study suggests that targeted skeletal gene panel sequencing is highly sensitive for prenatal diagnosis of fetuses presenting with unexpected ultrasound findings suggestive of a skeletal dysplasia.