Sequencing helped to diagnose 1/3 of fetuses with abnormalities

Review of data gathered by clinical diagnostic laboratory revealed that in past eight years, out of 146 sequencing procedures in one laboratory, a diagnosis has been based on genetic factors in 46 cases.

Only 13% of fetuses inherited detected variants from parents. 87% variants were de novo mutations.

Harmful variants were detected in genes: ACTA1, ADGRG6, ALG12, AR, C5orf42, CHRNG, COL11A1, COL1A1, COL1A2, COL4A1, DDX3X, DOK7, DVL1, DYNC2H1, EIF2B2, FBN1, FRMD4A, GLI3, HCCS, IFT80, INTU, KMT2D, KRAS, LAMC3, MID1, MYH3, NDUFAF5, NIPBL, P3H1, PEX1, PKD1L1, PTPN11, RAPSN, RIT1, RYR1, SOS1, TMEM67, TUBA1A, WDR19.

Most common pathogenic variants were those in the COL genes family. 5 cases associated cases displayed skeletal development abnormalities.

US Baylor Genetics laboratory between 2012 and 2017 have regularly attempted to diagnose disorders before birth with ultrasound imaging and sequencing of exome (genome regions accounting for proteins). During this period methods steadily evolved: from 12 weeks-long procedure in 2012 to 2 weeks-long procedure in 2017. Reduction of waiting time for diagnosis has a significant influence on pregnancy decision-making.

This is the first review of fetus exome sequencing with a large sample size. The findings are close to a review of 278 neonates/infants genome sequencing procedures in intensive care units, where exome sequencing backed 36,7% of recently born patients.

More: “Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder”, E. Normand et al., 2018, doi.org/10.1186/s13073-018-0582-x.