Table 2.
Fetal sequencing results.
| Fetal diagnosis | Inheritance | Gene variant(s) | Variant classification Case classification |
|---|---|---|---|
| AD, Ectrodactyly, ectodermal dysplasia, cleft/lip | Parental mosaicism |
TP63 NM_003722.4:c.1028G>A [p.Arg343Pro] |
Pathogenic Positive-definitive |
| AR, Meckel-Grubera | Compound heterozygous |
TMEM67 NM_153704.5:c.579_580del [p.Gly195fs] NM_153704.5:c.622A>T [p.Arg208Ter] |
Pathogenic/pathogenic Positive-definitive |
| AR, Meckel syndrome 4 | Compound heterozygous |
CEP290 NM_025114.3:c.1936C>T [p.Gln646Ter] NM_025114.3:c.384_387del [p.Asp128Glufs] |
Pathogenic/pathogenic Positive-definitive |
| Somatic, CLOVES | De novo, somatic |
PIK3CA NM_006218.3:c.3140A>G [p.His1047Arg] |
Pathogenic Positive-definitive |
| AD, Distal arthrogryposis type 2B | De novo |
TNNT3 NM_006757.3:c.188G>A [p.R63H] |
Pathogenic Positive-definitive |
| AD, CHARGE | De novo |
CHD7 NM_017780.3:c.282delT [p.Asn96fs] |
Pathogenic Positive-definitive |
| AD, Branchio-oculofacial syndrome (BOFS) | De novo |
TFAP2A NM_001032280.2:c.1154T>G [p.Val385Gly] |
Likely pathogenic Positive-probable |
| AD, Malformations of cortical development, polymicrogyria and microcephaly | De novo |
DYNC1H1 NM_001376.4:c.7999A>G [p.Asn2667Asp] |
Likely pathogenic Positive-probable |
| AD, Osteogenesis imperfectaa | De novo |
COL1A1 NM_000088.3:c.1875+1G>A |
Likely pathogenic Positive-probable |
| AD, Scalp-ear-nipple syndromea | De novo |
KCTD1 NM_001258221.1:c.86A>G [p.N29S] |
Likely pathogenic Positive-Probable |
| AD, Renal hypoplasia/aplasia | Compound heterozygous |
GREB1L NM_001142966.2:c.4881_4882del [p.H1627fs] |
Likely pathogenic Positive-Probable |
| AR, Smith-Lemli-Opitz | Compound heterozygous |
DHCR7 NM_001360.2:c.964-1G>C NM_001360.2:c.439G>A [p.Gly147Ser] |
Pathogenic/likely pathogenic Positive-Probable |
| AR, Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 | Compound heterozygous |
WDR81 NM_001163809.1:c.218del [p.G74fs] NM_001163809.1:c.2836_2839del [p.F946fs] |
Likely pathogenic/likely pathogenic Positive-Probable |
| AD, Noonan syndrome, cardiofaciocutaneous syndrome | De novo |
KRAS NM_004985.3:c.204G>C [p.Arg68Ser] |
Likely pathogenic Positive-Probable |
| AD, Wiedemann-Steiner syndrome | De novo |
KMT2A NM_001197104.1:c.10498C>T [p.Gln3500Ter] |
Likely pathogenic Positive-Probable |
| AD, Hereditary lymphedema 1A | De novo |
FLT4 NM_182925.4:c.3823A>G [p.Ser1275Gly] |
Likely pathogenic Positive-Probable |
| AD, Spinocerebellular ataxia, Gillespie syndrome | De novo |
ITPR1 NM_001168272.1:c.7591G>A [p.Val2531Met] |
Likely pathogenic Positive-Probable |
| AD, Congenital myopathy, Costello syndrome AR, Sandhoff disease |
De novo; compound heterozygous |
HRAS NM_005343.3:c.35G>T [p.G12V] HeXB (positive diagnosis by amniotic fluid enzyme analysis) NM_000521.3:c.668T>C [p.Leu223Pro] NM_000521.3:c.715G>A [p.Val239Ile] |
Likely pathogenic Positive-Probable Likely pathogenic/likely pathogenic Positive-Probable |
| AR, AD Renal tubular dysgenesis | Homozygous |
REN NM_000537.3:c.492+1G>A |
Likely pathogenic Positive-Probable |
| AD, Lymphedema-distichiasis syndrome | Parental inheritance |
FOXC2 NM_005251.2:c.612del [p.Pro204fs] |
Likely pathogenic Positive-Probable |
| X-linked dominant, Craniofrontonasal dysplasia | De novo |
EFNB1 NM_004429.4:c.190T>A [p.Cys64Ser] |
Likely pathogenic Positive-Probable |
| AR, Glycogen storage disease IV | Compound heterozygous |
GBE1 NM_000158.3:c.563A>C [p.His188Pro] NM_000158.3:c.1618+1G>A |
Likely pathogenic/VUS Inconclusive-possible |
| AR, Bardet-Biedl | Compound heterozygous |
BBS12 NM_001178007.1:c.104C>A [p.Ser35*] NM_001178007.1:c.1996_1998del [p.Val666del] |
Pathogenic/VUS Inconclusive-possible |
| AR, Short rib polydactyly | Compound heterozygous |
DYNC2H1 NM_001080463.1:c.9044A>G [p.Asp3015Gly] Intragenic tandem duplication detected by FISH |
Likely pathogenic/VUS Inconclusive-possible |
| AR, Fetal akinesia deformation sequencea | Compound heterozygous |
MUSK NM_005592.3:c.1724T>C [p.Ile575Thr] NM_005592.3:c.2408A>G [p.Tyr803Cys] |
Pathogenic/VUS Inconclusive-possible |
| AD, Lymphedema-distichiasis syndrome | Parental inheritance |
FOXC2 NM_005251.2:c.251C>T [p.Ala84Val] |
VUS Inconclusive-possible |
| AR, Hereditary lymphedemaa | Compound heterozygous |
PIEZO1 NM_001142864.3:c.7129+1G>C NM_001142864.3:c.307C>T [p.Arg103Ter] |
Likely pathogenic/VUS Inconclusive-possible |
| AR, Lethal congenital contracture syndrome 9 | Homozygous |
GPR126 (ADGRG6) NM_198569.2:c.2515C>T [p.His839Tyr] |
VUS Inconclusive-possible |
| AR, Seckel syndrome 9 | Compound heterozygous |
TRAIP NM_005879.2:c.553C>T [p.R185*] NM_005879.2:c.140C>T [p.P47L] |
VUS/pathogenic Inconclusive-possible |
| AR, Short rib polydactylya | Compound heterozygous |
DYNC2H1 NM_001080463.1:c.10594C>T [p.Arg3532Ter] NM_001080463.1:c.8012T>C [p.Met2671Thr] |
VUS/likely pathogenic Inconclusive-possible |
| AR, Congenital disorder of glycosylation, type Id | Compound heterozygous |
ALG3 NM_005787.5:c.487C>T [p.R163C] NM_005787.5:c.1154G>C [p.R385T] |
VUS/VUS Inconclusive-possible |
AD autosomal dominant, AR autosomal recessive, FISH fluorescence in situ hybridization, VUS variant of uncertain significance.
a
Previously reported in our pilot study.2