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Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (1): 7-11    DOI: 10.31083/j.ceog.2020.01.4910
Original Research Previous articles | Next articles
Mutation analysis of the fibroblast growth factor receptor 3 gene in fetuses with thanatophoric dysplasia, type I
Q.C. Wu1, *(), W.B. Wang1, L. Sun1, Y.S. Xu1, X.J. Xie1, X.M. Ma1, Z.Y. Su1
1Prenatal Diagnosis Center of Xiamen's Maternal & Child Health Care Hospital, Xiamen City, Fujian Province, China
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Abstract  

Objective: To analyze the fibroblast growth factor receptor 3 gene (FGFR3) mutations in fetuses with thanatophoric dysplasia type I (TD1) and to provide additional data for genotype-phenotype analyses. Materials and Methods: Eight cases of severe fetal short-limb dwarfism detected by antenatal ultrasonography were referred to this center. Before the termination of pregnancy, cordocentesis was performed for FGFR3 gene-sequencing analysis. Postmortem radiographic examination was performed in each instance for definitive diagnosis. Results: By FGFR3 gene sequencing, the authors identified six cases with missense mutations and two cases with stop codon mutations in the FGFR3 gene. Among the 6 FGFR3 missense mutations, four cases revealed a heterozygous p.Arg248Cys mutation, one case had a heterozygous p. Tyr373Cys mutation, and one case had a heterozygous p.Ser348Cys mutation. Discussion: The present data confirm the existence of hotspot FGFR3 mutations of TD1 and suggest that considerable overlap may occur between genotypes and phenotypes among FGFR3-related skeletal dysplasias.

Key words:  Thanatophoric dysplasia      FGFR3 gene      Mutation      Prenatal diagnosis     
Published:  15 February 2020     
*Corresponding Author(s):  Q.C. Wu     E-mail:  qichang_wu@163.com

Cite this article: 

Q.C. Wu, W.B. Wang, L. Sun, Y.S. Xu, X.J. Xie, X.M. Ma, Z.Y. Su. Mutation analysis of the fibroblast growth factor receptor 3 gene in fetuses with thanatophoric dysplasia, type I. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(1): 7-11.

URL: 

https://ceog.imrpress.com/EN/10.31083/j.ceog.2020.01.4910     OR     https://ceog.imrpress.com/EN/Y2020/V47/I1/7

Table 1  — Characteristics of eight referrals and evaluation of their findings.
Case Maternal age (y) Gestational age (weeks) Ultrasound findings Radiographic diagnosis Molecular analysis results
1 28 26 + 2 BPD: 7.2 cm, FL: 1.9 cm, HL: 1.7 cm TD1, Figure 1(a) c.1118A>G, p.Tyr373Cys
2 27 26 BPD: 7.8 cm, FL: 2.3 cm, HL: 2.1 cm TD1, Figure 1(b) c.742C>T, p.Arg248Cys
3 25 23 + 1 BPD: 5.7 cm, FL: 1.8 cm, HL: 1.8 cm TD1, Figure 1(c) c.742C>T, p.Arg248Cys
4 34 25 + 3 BPD, 7.6 cm: FL, 1.9 cm: HL, 2.0 cm TD1, Figure 1(d) c.742C>T, p.Arg248Cys
5 26 24 + 2 BPD: 6.0 cm, FL: 1.9 cm, HL: 2.0 cm TD1, Figure 1(e) c.2419T>G, p.Ter807Gly
6 38 25 + 4 BPD: 6.8 cm, FL: 2.0 cm, HL: 2.0 cm TD1, Figure 1(f) c.2421A>C, p.Ter807Cys
7 33 24 BPD: 5.9 cm, FL: 1.7 cm, HL: 1.7 cm TD1, Figure 1(g) c.742C>T, p.Arg248Cys
8 34 25 + 2 BPD: 6.4 cm, FL: 1.9 cm, HL: 2.0 cm TD1, Figure 1(h) c.1043C>G, p.Ser348Cys
Figure 1.  — Differential radiological features such as very short, curved long bones, short ribs without fracture, severe platyspondyly, and a normal skull without a clover-leaf shape are present in all cases, which is consistent with the diagnosis of TD1.

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