title: Detection of a de novo Y278C mutation in FGFR3 in a pregnancy with severe fetal hypochondroplasia: prenatal diagnosis and literature review.
abstract: OBJECTIVE
  We describe a prenatal molecular diagnosis of hypochondroplasia (HCH) in a pregnancy not at risk of HCH and review the literature on prenatal diagnosis of HCH.
  
  
  METHODS
  A 28-year-old primigravid woman was referred for genetic counseling at 30 weeks of gestation because of short-limbed dwarfism in the fetus. The woman had a body height of 152 cm. Her husband had a body height of 180 cm. Level II ultrasound showed a normal amount of amniotic fluid and a singleton fetus with fetal biometry equivalent to 30 weeks except for short limbs. Fetal biometry measurements were as follows: biparietal diameter = 7.38 cm (30 weeks); head circumference = 28.14 cm (30 weeks); abdominal circumference (AC) = 24.64 cm (30 weeks); femur length (FL) = 3.97 cm (<5th centile); FL/AC ratio = 0.161 (normal > 0.18); humerus = 3.64 cm (<5th centile); radius = 3.49 cm (30 weeks); ulna = 3.76 cm (<5(th) centile); tibia = 3.67 cm (<5th centile); and fibula = 3.72 cm (<5th centile). The digits and craniofacial appearance were normal. A tentative diagnosis of achondroplasia (ACH) was made. DNA testing for the FGFR3 gene and whole-genome array comparative genomic hybridization (aCGH) analysis were performed using cord blood DNA obtained by cordocentesis. FGFR3 mutation analysis revealed a de novo heterozygous c.833A > G, TAC > TGC transversion in exon 7 leading to a p.Tyr278Cys (Y278C) mutation in the FGFR3 protein. aCGH analysis revealed no genomic imbalance in cord blood. After delivery, the fetus had short limbs, a narrow thorax, brachydactyly, and relative macrocephaly. Cytogenetic analysis of cultured placental cells revealed a karyotype of 46,XX.
  
  
  CONCLUSIONS
  Prenatal diagnosis of abnormal ultrasound findings suspicious of ACH should include a differential diagnosis of HCH by molecular analysis of FGFR3.
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: cpc_mmh@yahoo.com.
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Taipei Medical University, Taipei, Taiwan; Dianthus MFM Clinic, Taipei, Taiwan.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tzu-Hung
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Taiji Fetal Medicine Center, Taipei, Taiwan.
authors.forename: Tung-Yao
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Su
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Bioengineering, Tatung University, Taipei, Taiwan.
authors.forename: Wayseen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000130:Achondroplasia / Q000175:diagnosis*; D000328:Adult; D001842:Bone and Bones / Q000002:abnormalities* / Q000000981:diagnostic imaging; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004392:Dwarfism / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D017880:Limb Deformities, Congenital / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D008141:Lordosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D009154:Mutation; D011247:Pregnancy; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D016216:Ultrasonography, Prenatal
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: FGFR3; hypochondroplasia; prenatal diagnosis