Skip to main content

Table 2 Fetal molecular diagnoses

From: Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder

Case ID Gene Variants [RefSeq ID] Inheritance/zygosity Clinical impact Pre-test recurrence risk Post-test recurrence risk Disease association(s) [MIM #]
30-P ACTA1 c.116G>A (p.R39H)
[NM_001100]
AD/de novo het NR NR RES Nemaline myopathy 3 [MIM: 161800]; Myopathy, congenital, with fiber-type disproportion 1 [MIM: 255310]
24-P ADGRG6 c.2677C>T (p.R893X)
[NM_020455]
AR/homozygous Reproductive planning NR 25% Lethal congenital contracture syndrome 9 [MIM: 616503]
8-P ALG12 c.437G>A (p.R146Q)
c.930_931delAC (p.R311fs)
[NM_024105]
AR/compound het Reproductive planning NR 25% Congenital disorder of glycosylation type 1G [MIM: 607143]
111-T AR c.1814A>G (p.D605G)
[NM_000044]
XL/hemizygous (maternally inherited) Reproductive planning
Recurrence risk
Unknown 50% (males) Complete androgen insensitivity syndrome [MIM: 300068]
43-PRE C5orf42 c.3667C>T (p.Q1223X)
c.1372-2A>G
[NM_023073]
AR/compound het NR NR 25% Orofaciodigital syndrome 6 [MIM: 277170]; Joubert syndrome 17 [MIM: 614615]
87-PRE CHRNG c.136C>T (p.R46X)
c.459dupA (p.V154fs)
[NM_005199]
AR/compound het NR NR 25% Multiple pterygium syndrome, lethal type [MIM: 253290]; Multiple pterygium syndrome, Escobar variant [MIM: 265000]
80-T COL11A1 c.2739_2747del (p.P914_G916del)
[NM_001854]
AD/de novo het NR NR RES Stickler syndrome 2 [MIM: 604841]; Marshall syndrome [MIM: 154780]; Fibrochondrogenesis 1 [MIM: 228520]
17-P COL1A1 c.2110G>A (p.G704S)
[NM_000088]
AD/de novo het NR NR RES Osteogenesis imperfecta (OI) types 1–4 [MIM: 166200, 166210, 259420, 166220]; Caffey disease [MIM: 114000]; Ehlers-Danlos syndrome 1 and 7a [MIM: 130000, 130060]
49-T COL1A1 c.2533G>A (p.G845R)
[NM_000088]
AD/de novo het Recurrence risk Up to 25% RES Osteogenesis imperfecta (OI) types 1–4 [MIM: 166200, 166210, 259420, 166220]; Caffey disease [MIM: 114000]; Ehlers-Danlos syndrome 1 and 7a [MIM: 130000, 130060]
90-PRE COL1A1 c.2164G>A (p.G722S)
[NM_000088]
AD/de novo het Medical management
Reproductive planning
Recurrence risk
Up to 25% RES Osteogenesis imperfecta (OI) types 1–4 [MIM: 166200, 166210, 259420, 166220]; Caffey disease [MIM: 114000]; Ehlers-Danlos syndrome 1 and 7a [MIM: 130000, 130060]
65-PRE COL1A2 c.1378G>A (p.G460S)
[NM_000089]
AD/de novo het Recurrence risk Up to 50% RES Osteogenesis imperfecta types 2–4 [MIM: 166210, 259420, 166220]; Ehlers-Danlos syndrome types 7B and cardiac valvular [MIM: 130060, 225320]
66-PRE COL1A2 c.2576G>A (p.G859D)
[NM_000089]
AD/de novo het NR NR RES Osteogenesis imperfecta types 2–4 [MIM: 166210, 259420, 166220]; Ehlers-Danlos syndrome types 7B and cardiac valvular [MIM: 130060, 225320]
53-P COL4A1 c.2879G>T (p.G960V)
[NM_001845]
AD/inherited het (mosaic mother) Reproductive planning NR Up to 50% Brain small vessel disease with hemorrhage [MIM: 607595]; Hereditary angiopathy with nephropathy aneurysms and muscle cramps [MIM: 611773]; Porencephaly 1 [MIM: 175780];
122-T DDX3X c.1703C>T (p.P568L)
[NM_001193416]
XL, de novo het NR NR RES Mental retardation, X-linked 102 [MIM: 300958]
7-P DOK7 c.437C>T (p.P146L)
c.514G>A (p.G172R)
[NM_173660]
AR, compound het NR NR 25% Fetal akinesia deformation sequence [MIM: 208150]; Myasthenia, limb-girdle, familial [MIM: 254300]
101-PRE DVL1 c.1519delT (p.W507fs)
[NM_004421]
AD/de novo het NR NR RES Robinow syndrome, autosomal dominant 2 [MIM: 616331]
95-P DYNC2H1 c.10885C>T (p.R3629X)
c.11230C>T (p.L3744F)
[NM_001080463]
AR/compound het NR NR 25% Short-rib thoracic dysplasia 3 [MIM: 613091]
22-P EIF2B2 c.586C>T (p.P196S)
c.599G>T (p.G200V)
[NM_014239]
AR/compound het NR NR 25% Leukodystrophy with vanishing white matter [MIM: 603896]
81-PRE FBN1 c.3299G>T (p.G1100V)
[NM_000138]
AD/de novo het NR NR RES Marfan syndrome [MIM: 154700]; Geleophysic dysplasia 2 [MIM: 614185] MASS syndrome [MIM:604308]; Ectopia lentis, familial [MIM:129600]; Acromicric dysplasia [MIM:102370]; Marfan lipodystrophy syndrome [MIM: 616914]; Weill-Marchesani syndrome 2 [MIM: 608328]; Stiff skin syndrome [MIM:184900]
60-T FRMD4A c.2723C>T (p.S908L)
[NM_018027]
AR/homozygous NR NR 25% Agenesis of corpus callosum, with facial anomalies and cerebellar ataxia [MIM: 616819]
88-PRE GLI3 c.3324C>G (p.Y1108X)
[NM_000168]
AD/de novo het NR NR RES Pallister-Hall syndrome [MIM: 146510]; Greig cephalopolysyndactyly syndrome [MIM: 175700]; Polydactyly types A1 and B [MIM: 174200]; Polydactyly, type IV [MIM: 174700]
74-PRE HCCS c.308_309insAGT (p.V103dup)
[NM_005333]
XL/de novo het NR NR RES Linear skin defects with multiple congenital anomalies [MIM: 309801]
114-T IFT80 c.721G>C (p.G241R)
[NM_020800]
AR/homozygous Reproductive planning
Recurrence risk
Unknown 25% Short-rib thoracic dysplasia 2 with or without polydactyly [MIM: 611263]
96-P INTU c.1259+5G>T
c.1714C>T (p.R572X)
[NM_015693]
AR/compound het NR NR 25% Ciliopathy with features of short-rib polydactyly syndrome
6-P KMT2D c.6617dupC (p.A2207fs)
[NM_003482]
AD/de novo het Reproductive planning
Recurrence risk
Unknown RES Kabuki syndrome type 1 [MIM: 147920]
45-P KMT2D c.1967delT (p.L656fs)
[NM_003482]
AD/ het
(biological parents unavailable, gamete donors used)
Medical management
Recurrence risk
Up to 25% ~ 0%
(unless same donors used again)
Kabuki syndrome type 1 [MIM: 147920]
48-PRE KMT2D c.15680_15693dup (p.I5232fs)
[NM_003482]
AD/de novo het NR NR RES Kabuki syndrome type 1 [MIM: 147920]
126-PRE KMT2D c.5707C>T (p.R1903X)
[NM_003482]
AD/de novo het NR NR RES Kabuki syndrome type 1 [MIM: 147920]
55-PRE KRAS c.149C>T (p.T50I)
[NM_004985]
AD/de novo het NR NR RES Noonan syndrome 3 [MIM: 609942]; Cardiofaciocutaneous syndrome [MIM: 115150]
63-PRE LAMC3 c.4415G>A (p.R1472Q)
c.4477+1G>A
[NM_006059]
AR/compound het NR NR 25% Cortical malformations occipital [MIM: 614115]
47-T MID1 c.673_674delAG (p.S225X)
[NM_000381]
XL/hemizygous (inherited from mildly affected mother) NR NR 50% (males) Opitz GBBB syndrome 1 [MIM: 300000]
67-PRE MYH3 c.2015G>A (p.R672H)
[NM_002470]
AD/inherited het (mosaic mother) NR NR Up to 50% Arthrogryposis, distal types 2A, 2B, 8 [MIM: 193700, 601680, 178110]
20-P NDUFAF5 c.29T>A (p.L10X)
c.782T>G (p.M261R)
[NM_024120]
AR/compound het Reproductive planning
Other (see Results)
25% 25% Mitochondrial complex I deficiency [MIM: 252010]
1-P NIPBL c.459-2A>G
[NM_133433]
AD/de novo het Recurrence risk Unknown RES Cornelia de Lange syndrome type 1 [MIM: 122470]
112-PRE P3H1 c.12delC (p.R4fs)
[NM_022356]
AR/homozygous Reproductive planning
Recurrence risk
25–50% 25% Osteogenesis imperfecta 8 [MIM: 610915]
13-P PEX1 c.2097dupT (p.I700fs)
c.3205C>T (p.Q1069X)
[NM_000466]
AR/compound het Reproductive planning NR 25% Peroxisome biogenesis disorder types 1A, 1B [MIM: 214100, 601539]
46-PRE PKD1L1 c.6473+2_6473+3del
[NM_138295]
AR/homozygous NR NR 25% Heterotaxy, visceral, 8, autosomal [MIM: 617205]
85-PRE PTPN11 c.227A>T (p.E76V)
[NM_002834]
AD/de novo mosaic NR NR 0% Noonan syndrome 1 [MIM: 163950]; LEOPARD syndrome 1 [MIM: 151100]; Metachondromatosis [MIM: 156250];
144-PRE PTPN11 c.854T>C (p.F285S)
[NM_002834]
AD/de novo het Reproductive planning NR RES Noonan syndrome 1 [MIM: 163950]; LEOPARD syndrome 1 [MIM: 151100]; Metachondromatosis [MIM: 156250]
84-PRE RAPSN c.1166+1G>C
[NM_005055]
AR/homozygous NR NR 25% Fetal akinesia deformation sequence [MIM: 208150]; Myasthenic syndrome, congenital, 11 [MIM: 616326]
69-PRE RIT1 c.246T>G (p.F82L)
[NM_006912]
AD/de novo het NR NR RES Noonan syndrome 8 [MIM: 615355]
18-P RYR1 c.14344G>A (p.G4782R)
c.14512-1G>A
[NM_000540]
AR/compound het Medical management
Reproductive planning
25% 25% Central core disease of muscle [MIM: 117000]
133-PRE SOS1 c.1655G>A (p.R552K)
[NM_005633]
AD/de novo het NR NR RES Noonan Syndrome 4 [MIM: 610733]
11-P TMEM67 c.1319G>A (p.R440Q)
c.233G>A (p.C78Y)
[NM_153704]
AR/compound het Reproductive planning 25% 25% Meckel syndrome 3 [MIM: 607361]; Joubert syndrome 6 [MIM: 610688]; Bardet-Biedl syndrome [MIM: 209900]; COACH syndrome [MIM: 216360]; Nephronophthisis 11 [MIM: 613550]
44-PRE TUBA1A c.1118G>A (p.R373K)
[NM_006009]
AD/de novo het Reproductive planning Unknown RES Lissencephaly type 3 [MIM: 611603]
21-P WDR19 c.275T>G (p.L92X)
c.880G>A (p.G294R)
[NM_025132]
AR/compound het Medical management
Reproductive planning
Recurrence risk
Up to 25% 25% Short-rib thoracic dysplasia 5 [MIM: 614376]; Cranioectodermal dysplasia 4 [MIM: 614378]; Nephronophthisis 13 [MIM: 614377]
  1. Genes, variants, and diseases that contributed to the 46 molecular diagnoses from fetal exome sequencing. Case IDs ending in -PRE are prenatal trio exomes, those ending in -T are standard trio exomes, and those ending in -P are proband exomes
  2. Abbreviations: AD autosomal dominant, AR autosomal recessive, XL X-linked, het heterozygous, hom homozygous, hemi hemizygous, RES residual recurrence risk due to possibility of parental germline mosaicism, NR information not received from ordering physicians