Table 2.
Identification of genes associated with skeletal diseases in 30 cases of fetal skeletal dysplasia
| No. | Ultrasound results | Inheritance | Bone gene-encoded | Reference sequence | Nucleotide change/mutation | Amino-acid change | Genetic subregion | Heterogeneity | Chromosomal Loci | Mutation type | Sanger verification | Next pregnancy/child | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Paternal | Maternal | ||||||||||||
| 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 | |
Het heterogeneity, Pathogenic known disease-causing mutation, VUS Mutations of unknown clinical significance, N normal, AD autosomal dominant, AR autosomal recessive, PGD preimplantation genetic diagnosis