Identification of a De Novo Heterozygous Missense FLNB Mutation in Lethal Atelosteogenesis Type I by Exome Sequencing.
10.3343/alm.2014.34.2.134
- Author:
Ga Won JEON
1
;
Mi Na LEE
;
Ji Mi JUNG
;
Seong Yeon HONG
;
Young Nam KIM
;
Jong Beom SIN
;
Chang Seok KI
Author Information
1. Department of Pediatrics, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea.
- Publication Type:Case Reports ; Research Support, Non-U.S. Gov't
- Keywords:
Atelosteogenesis type I;
FLNB;
Mutation;
Exome sequencing
- MeSH:
Exome;
Female;
Filamins/chemistry/*genetics;
Gene Frequency;
Heterozygote;
Humans;
Infant, Newborn;
Mutation, Missense;
Osteochondrodysplasias/*genetics/pathology/radiography;
Polymorphism, Single Nucleotide;
Sequence Analysis, DNA
- From:Annals of Laboratory Medicine
2014;34(2):134-138
- CountryRepublic of Korea
- Language:English
-
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.
