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

From: Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases

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  
  1. 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