Table 2 Identification of genes associated with skeletal diseases in 30 cases of fetal skeletal dysplasia

1

Right choroid plexus cyst and left foot inversion in the fetus

Trisomy 18

Delivered a healthy child

2

Absence of radius in the upper limbs of the fetus, abnormal posture of both hands

Trisomy 18

Delivered a healthy child

3

Continuously interrupted left upper lip, broken upper alveolar bone, possible small jaw, and absent fetal femur

AD

TBX4

NM_018488.2

c.1200G > T

p.Glu400Asp

EX8E

Het

Chr17:59560439

VUS

N

Het

4

Spinal fissure (isopathology), gastroschisis, double lung dysplasia, bipedal varus, left foot polydactyly

AD

TNNT3

NM_006757.3

c.88G > A

p.Ala30Thr

EX7

Het

Chr 11:1950355

VUS

Het

N

Delivered a healthy child

5

Bending bilateral femur, tibia and fibula, fixed knee, internal crossed flexion, and fixed foot position

AD

SOX9

NM_000346.3

c.344G > C

p.Trp115Ser

EX1

Het

Chr17:70117876

VUS

N

N

Delivered a healthy child

6

Cleft lip and palate, right kidney cystic dysplasia, bilateral foot fissure, and syndactyly, partially absent fingers of both hands

AD

TP63

NM_003722.4

c.952C > T

p.Arg318Cys

EX7

Het

Chr3:189585691

Pathogenic

N

N

7

Fetal bilateral femoral angulation deformity, fetal heart ventricular septal defect

AR

POR

NM_000941.2

c.1370G > A

p.Arg457His

EX12

Het

Chr7: 75614497

Pathogenic

N

Het

Angular femoral deformity found at the 15th week of pregnancy, pregnancy terminated

c.744C > G

p.Tyr248*

EX8

Het

Chr7: 75611554

Pathogenic

Het

N

8

Right foot inversion, bilateral rocker bottom feet, scoliosis, spina bifida occulta

AR

CHRNG

NM_005199

C.13C > T

p.Q5X,513

EX1

Het

Chr2

Pathogenic

N

Het

Same abnormality as the previous pregnancy, undergoing PGD

C.202C > T

p.R68X,450

EX3

Het

Chr2

Pathogenic

Het

N

9

Fetal scoliosis, fetal bipedal varus, ventricular septal defect

No abnormalities

10

Absence of bilateral ulna and radius, absence of bilateral humerus, foot inversion, abnormal wrist joints

No abnormalities

11

Absence of bilateral humerus and left foot

No abnormalities

12

Only two visible metacarpal bones on the left hand and part of distal phalanx on the lateral and medial sides

No abnormalities

13

Left foot inversion, absence of right lower limb

No abnormalities

14

Absence of fetal fibula, foot inversion, partial absence of phalanges, absence of fingers, hand cleft deformity

No abnormalities

Delivered a healthy child

15

Fetal sirenomelia

No abnormalities

Delivered a healthy child

16

Short limbs - incomplete osteogenesis?

AD

COL1A1

NM_000088.3

c.1678G > A

p.Gly560Ser

EX25

Het

Chr17: 48268739

Pathogenic

N

N

17

Short limbs - incomplete osteogenesis

AD

COL1A2

NM_000089.3

c.1774G > A

p.Gly592Ser

EX31

Het

Chr7: 94045726

Pathogenic

N

N

18

Short limbs

AD

COL1A2

NM_000089.3

c.1072G > A

p.Gly358Ser

EX20

Het

Chr7: 94039590

Pathogenic

N

N

Delivered a healthy child

19

Short fetus limbs: cartilage hypoplasia?

AD

COL2A1

NM_001844.4

c.3013G > A

p.Gly1005Ser

CDS44

Het

Chr12:48371891

Pathogenic

N

N

20

Short limbs, spine and vertebral ossification are not obvious: cartilage hypoplasia?

AD

COL2A1

NM_001844.4

c.2419G > A

p.Gly807Arg

EX37

Het

Chr12:48375170

VUS

N

N

21

Short limbs, ventricular septal defect

AD/

AR

COL11A2

NM_080680.2

c.966dupC

p.Thr323Hisfis*19

EX8

Het

Chr6:33152074

Pathogenic

Het

N

Undergoing PGD

c.1773 + 8 T>A

–

IVS19

Het

Chr6:33146204

VUS

N

Het

22

Abnormal long bones in fetal limbs, narrow chest

XD

EBP

NM_006579.2

c.440G>A

p.Arg147His

EX4

Het

ChrX:48385644

Pathogenic

N

N

Delivered a healthy boy

23

Short fetal limbs (chronic dysgenesis)

AD

FGFR3

NM_001163213.1

c.742C > T

p.Arg248Cys

EX7

Het

Chr4:1803564

Pathogenic

N

N

Delivered a healthy child

24

Short limbs (cartilage hypoplasia)

AD

FGFR3

NM_001163213.1

c.742C > T

p.Arg248Cys

EX7

Het

Chr4:1803564

Pathogenic

N

N

25

Short limbs

AD

FGFR3

NM_001163213.1

c.742C > T

p.Arg248Cys

EX7

Het

Chr4:1803564

Pathogenic

N

N

26

Short limbs

AD

FGFR3

NM_001163213.1

c.742C > T

p.Arg248Cys

EX7

Het

Chr4:1803564

Pathogenic

N

N

27

Short limbs

AD

FGFR3

NM_001163213.1

c.1144G > A

p.Gly382Arg

EX9

Het

Chr4:1806119

Pathogenic

N

N

28

Short limbs

AD

FGFR3

NM_001163213.1

c.1124A > G

p.Tyr375Cys

EX9

Het

Chr4:1806099

Pathogenic

N

N

29

Achondroplasia

AD

FGFR3

NM_001163213.1

c.2426G > C

p.X809S,101

EX18

Het

Chr4:1806099

Pathogenic

N

N

30

Uneven arrangement of fetal spine, short limbs, bilateral foot inversion, small mandibular, left ventricular punctate strong echo, ventricular septal defect

AD

FLNB

NM_001164317.1

c.475A > C

p.Thr159Pro

EX2

Het

Chr3:58062955

VUS

N

N