Table 1 Fetal phenotypes and identified pathogenic and likely pathogenic variants in our cohort.
No. | Fetal phenotype | Gene | Variant | Reference sequence | Zygosity/inheritance | ACMG classification/criteria** | Disorder | Novel/known variant | ClinVar ID |
|---|---|---|---|---|---|---|---|---|---|
1 | NT > 3,5 mm, microgenia, mesomelia, syndactyly of fingers | SF3B4 | c.763_781del, p.(Pro255Cysfs*59) | NM_005850.4 | het, AD, unknown | 5 PVS1/PM2-M/PP3-S | Acrofacial dysostosis 1, Nager type | Novel | SCV001519055 |
2 | Hydrocephalus (2nd pregnancy with the same malformations) | MPDZ | c.4171C>T, p.(Arg1391Ter) | NM_001330637.1 | comp het, AR | 5 | Hydrocephalus, congenital, 2, w/wo brain or eye anomalies | Known | VCV000667381 |
c.5125_5126ins, p.(Tyr1709Cysfs*5) | 5 PVS1/PM2-M/PP3-S | Novel | SCV001519056 | ||||||
3* | Bilateral renal agenesia | ANOS1 | c.774del, p.(Trp258Cysfs*9) | NM_000216.3 | hemi, XL, mat inherited | 5 | Hypogonadotropic hypogonadism 1 w/wo anosmia (Kallmann syndrome 1) | Known | SCV001519057 |
4* | Left-sided diaphragmatic hernia, ascites, pleural efussion, susp. duplex kidneys | PTPN11 | c.218C>T, p.(Thr73Ile) | NM_002834.4 | het, AD, de novo | 5 | Noonan syndrome 1 | Known | VCV000013334 |
5 | Shortened limbs, multiple fractures | COL1A2 | c.1352G>A, p.(Gly451Asp) | NM_000089.3 | het, AD, de novo | 5 PP3-S/PS2-S/PM2-M/PP2-S | Osteogenesis imperfecta | Novel | SCV001519058 |
6* | NT > 7 mm, heart defect, multicystic dysplastic kidneys, shortened long bones, bilateral clubfoot, abnormal skull configuration | COL27A1 | c.4519C>T, p.(Arg1507Ter) | NM_032888.3 | hom, AR | 5 PVS1/PM2-M/PP3-S | Steel syndrome | Novel | SCV001519059 |
PKD1 | c.3984G>C, p.(Trp1328Cys) | NM_001009944.2 | hom, AD | 4 PM1-M/PM2-M/PP2-S/PP3-S | Polycystic kidney disease 1 | Novel | SCV001519060 | ||
7* | Fetal hydrops | GUSB | c.1084_1110del, p.(Asp362_Phe370del) | NM_000181.3 | comp het, AR | 4 | Mucopolysaccharidosis VII | Known | SCV001519061 |
c.1651C>T, p.(Gln551Ter) | 5 PVS1/PM2-M/PP3-S | Novel | SCV001519062 | ||||||
8* | Skeletal dysplasia, IUGR (length of long bones and fetal weight < 3rd percentile, small thorax) | CUL7 | c.5022_5025del, p.(Cys1674Trpfs*44) | NM_001168370.1 | hom, AR | 5 PVS1/PM2-M/PP3-S | 3-M syndrome 1 | Novel | SCV001519063 |
9* | Agenesis of corpus callosum, cerebellar hypoplasia, colpocephaly, transposition of great vessels, micropenis, fingers closed in fists, asymmetric shortened legs und malformed feet (2nd pregnancy with the same malformations) | COG6 | c.511C>T, p.(Arg171Ter) | NM_020751.2 | hom, AR | 5 | Congenital disorder of glycosylation, type IIl/Shaheen syndrome | Known | VCV000493007 |
10 | Skeletal dysplasia, shortened long bones, bilateral clubfoot | SLC26A2 | c.1020_1022del, p.(Val341del) | NM_000112.3 | comp het, AR | 4 | Diastrophic dysplasia/Achondrogenesis 1B/ | Known | VCV000065558 |
c.1957T>A, p.(Cys653Ser) | 5 | Atelosteogenesis, type II | Known | VCV000004098 | |||||
11 | Skeletal dysplasia, shortened long bones | SLC26A2 | c.749A>T, p.(Asp250Val) | NM_000112.3 | comp het, AR | 4 PM1-M/PM2-M/PM3-M/PP2-S/PP3-S | Diastrophic dysplasia/Achondrogenesis 1B/Atelosteogenesis, type II | Novel | SCV001519064 |
c.835C>T, p.(Arg279Trp) | 5 | Known | VCV000004089 | ||||||
12* | Polycystic kidneys, polyhydramnios | HNF1B | c.494G>A, p.(Arg165His) | NM_000458.3 | het, AD, de novo | 5 | Renal cysts and diabetes syndrome | Known | VCV000012647 |
13 | Agenesis of corpus callosum, hydronephrosis, bilateral clubfoot, abnormal hand position | KAT6B | c.3903del, p.(Ser1303Valfs*31) | NM_012330.3 | het, AD, de novo | 4 PVS1/PS2-S/PM2-M | Genitopatellar syndrome/SBBYSS syndrome | Novel | SCV001519065 |
14a | Multicystic, dysplastic enlarged kidneys, extreme oligohydramnios | KMT2D | c.5642_5644+1del, p.(?) | NM_003482.3 | het, AD, de novo | 5 PVS1/PS2-S/PM2-M/PP3-S | Kabuki syndrome 1 | Novel | SCV001519066 |
15 | Polycystic kidneys, dextrocardia | BBS2 | c.263del, p.(Gly88Alafs*6) | NM_031885.3 | hom, AR | 5 | Bardet-Biedl syndrome 2 | Known | VCV000217434 |
16 | Thanatophoric dysplasia | COL2A1 | c.2798G>A, p.(Gly933Glu) | NM_001844.4 | het, AD, de novo | 5 PS2-S/PM1-M/PM2-M/PP2-S/PP3-S | Platyspondylic lethal skeletal dysplasia, Torrance type/Achondrogenesis 2 | Novel | SCV001519067 |
17 | Brain malformation, bilateral clubfoot, pericardial effusion | VANGL1 | c.838del, p.(Leu280Ter) | NM_138959.2 | het, AD, de novo | 5 PVS1/PS2-S/PM2-M/PP3-S | Caudal regression syndrome/Neural tube defects, susceptibility to | Novel | SCV001519068 |
18b | Shortened long bones (< 3 percentille) | MN1 | c.3555C>A, p.(Cys1185Ter) | NM_002430.2 | het, AD, de novo | 5 PVS1/PS2-S/PM2-M/PP3-S | MN1-associated syndrome, CEBALID syndrome | Novel | SCV001519069 |
19# | NT > 3.5 mm, hydronephrosis, polycystic kidney, clubfoot, macrosomia, twin pregnancy, only one fetus with malformations | GPC3 | c.175+1G>T, p.(?) | NM_004484.3 | hemi, XL, mat inherited | 5 PVS1/PM2-M/PP3-S | Simpson-Golabi-Behmel syndrome, type 1 | Novel | SCV001519070 |
20 | Microcephaly, agenesis of the right kidney | NBN | c.657_661del, p.(Lys219Asnfs*16) | NM_002485.4 | hom, AR | 5 | Nijmegen breakage syndrome | Known | VCV000006940 |
21 | Brain malformations, cardiomegaly (2nd pregnancy with the same malformations) | TREX1 | c.236_243dup, p.(Ser82Leufs*9) | NM_033629.5 | hom, AR | 5 | Aicardi-Goutieres syndrome 1 | Known | SCV001519071 |
22c | Suspected fetal ciliopathy, cerebellar vermis hypoplasia, hyperechogenic enlarged kidneys, oligohydramnios (3rd pregnancy with similar malformations) | EXOC3L2 | c.(90+1_91-1)_(404+1_405-1)del, p.(?) | NM_138568.3 | hom, AR | 5 PVS1 | No OMIM disease association Publications: Meckel-Gruber-like syndrome | Novel | SCV001519072 |
23 | Lissencephaly | PEX1 | c.1587+1G>A, p.(?) | NM_000466.2 | comp het, AR | 5 | Peroxisome biogenesis disorder 1 A/1B | Known | VCV000371701 |
c.2875C>T, p.(Arg959Ter) | 5 | Known | VCV000371716 | ||||||
24 | Fetal hydrops, mild ventriculomegaly, microstomia, short fingers, syndyctyly of all fingers on the one hand side, heart malformation, shortend long bones, bilateral curved femur bones | FRAS1 | c.4259G>A, p.(Trp1420Ter) | NM_025074.6 | comp het, AR | 5 PVS1/PM2-M/PP3-S | Fraser syndrome 1 | Novel | SCV001519073 |
c.6433C>T, p.(Arg2145Ter) | 5 PVS1/PM2-M/PP3-S | Novel | SCV001519074 | ||||||
25 | Suspected brain and brain vessel malformations, further abnormalities not specified | PTEN | c.131G>A, p.(Gly44Asp) | NM_000314.6 | het, AD, mat inherited | 5 | Cowden syndrome 1/Macrocephaly and autism syndrome | Known | VCV000427582 |
PTPN11 | c.922A>G, p.(Asn308Asp) | NM_002834.4 | het, AD, de novo | 5 | Noonan syndrome 1 | Known | VCV000013326 | ||
26d | Fetal hydrops, hydrocephalus, multicystic, dysplastic kidneys, lung hypoplasia, cardiomyopathy, retrognathia | CDK10 | c.608+1G>A, p.(?) | NM_052988.4 | hom, AR | 5 | Al Kaissi syndrome | Known | VCV000440757 |
27 | Complex heart defect | KMT2D | c.11320C>T, p.(Gln3774Ter) | NM_003482.3 | het, AD, de novo | 5 PVS1-S/PS2-S/PM2-M/PP3-S | Kabuki syndrome 1 | Novel | SCV001519075 |
28 | Suspected skeletal dysplasia, shortened long bones, bilateral curved femurs, malformed thorax with bowed rips | COL1A1 | c.1201G>A, p.(Gly401Ser) | NM_000088.3 | het, AD, de novo | 5 | Osteogenesis imperfecta | Known | VCV000425596 |
29 | Agenesis of corpus callosum | DCC | c.3073C>T, p.(Arg1025Ter) | NM_005215.3 | het, AD, mat inherited | 5 PVS1/PM2-M/PP3-S | Mirror movements 1 and/or agenesis of the corpus callosum | Novel | SCV001519076 |
30 | Skeletal dysplasia | COL1A1 | c.1930G>A, p.(Gly644Ser) | NM_000088.3 | het, AD, de novo | 5 | Osteogenesis imperfecta, type II or III or IV | Known | VCV000392573 |
31 | Multiple malformations with contraction of distal muscles of the hands, bilateral clubfoot, minimal skin edema | NEB | c.24871-1G>C, p.(?) | NM_001271208.1 | hom, AR | 5 PVS1/PM2-M/PP3-S | Nemaline myopathy 2 | Novel | SCV001519077 |
