Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Identification of a De Novo Heterozygous Missense FLNB Mutation in Lethal Atelosteogenesis Type I by Exome Sequencing

  • Jeon, Ga Won (Department of Pediatrics, Inje University College of Medicine, Busan Paik Hospital) ;
  • Lee, Mi-Na (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jung, Ji Mi (Department of Pediatrics, Inje University College of Medicine, Busan Paik Hospital) ;
  • Hong, Seong Yeon (Department of Obstetrics and Gynecology, Catholic University of Daegu, Daegu Catholic University Medical Center) ;
  • Kim, Young Nam (Department of Obstetrics and Gynecology, Inje University College of Medicine, Busan Paik Hospital) ;
  • Sin, Jong Beom (Department of Pediatrics, Inje University College of Medicine, Busan Paik Hospital) ;
  • Ki, Chang-Seok (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2013.06.28
  • Accepted : 2013.12.26
  • Published : 2014.03.02
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Abstract

Background: Atelosteogenesis type I (AO-I) is a rare lethal skeletal dysplastic disorder characterized by severe short-limbed dwarfism and dislocated hips, knees, and elbows. AO-I is caused by mutations in the filamin B (FLNB) gene; however, several other genes can cause AO-like lethal skeletal dysplasias. Methods: In order to screen all possible genes associated with AO-like lethal skeletal dysplasias simultaneously, we performed whole-exome sequencing in a female newborn having clinical features of AO-I. Results: Exome sequencing identified a novel missense variant (c.517G>A; p.Ala173Thr) in exon 2 of the FLNB gene in the patient. Sanger sequencing validated this variant, and genetic analysis of the patient's parents suggested a de novo occurrence of the variant. Conclusions: This study shows that exome sequencing can be a useful tool for the identification of causative mutations in lethal skeletal dysplasia patients.

Keywords

References

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