Prenatal diagnosis of skeletal dysplasias using a targeted skeletal gene panel.

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

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.