Identification of a De Novo Heterozygous Missense FLNB Mutation in Lethal Atelosteogenesis Type I by Exome Sequencing

다국어 초록 (Multilingual 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 dys- plasias simultaneously, we performed whole-exome sequencing in a female newborn hav- ing 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 identi- fication of causative mutations in lethal skeletal dysplasia patients.

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