Molecular defects identified by whole exome sequencing in a child with Fanconi anemia

Abstract

Fanconi anemia is a rare genetic disease characterized by bone marrow failure, multiple congenital malformations, and an increased susceptibility to malignancy. At least 15 genes have been identified that are involved in the pathogenesis of Fanconi anemia. However, it is still a challenge to assign the complementation group and to characterize the molecular defects in patients with Fanconi anemia. In the current study, whole exome sequencing was used to identify the affected gene(s) in a boy with Fanconi anemia. A recurring, non-synonymous mutation was found (c.3971C>T, p.P1324L) as well as a novel frameshift mutation (c.989_995del, p.H330LfsX2) in FANCA gene. Our results indicate that whole exome sequencing may be useful in clinical settings for rapid identification of disease-causing mutations in rare genetic disorders such as Fanconi anemia.

Keywords: BFU-E; BRCA2/FANCD1; CFU-GM; CsA; DEB; ESP; Exome Sequencing Project; FA; FANCA; Fanconi anemia; Fanconi anemia group A; HGMD; ICLs; IGV; Integrative Genomics Viewer; MLPA; MMC; Molecular diagnostics; Multiplex Ligation-Dependent Probe Amplification; NGS; PALB2/FANCN; PGD; SCGE; SNV; WES; Whole exome sequencing; breast cancer 2/Fanconi anemia group D1; burst forming unit-erythroid; colony forming unit-granulocyte, monocyte; cyclosporin A; diepoxybutane; interstrand cross-linking agents; mitomycin C; next generation sequencing; partner and localizer of BRCA2/Fanconi anemia group N; pre-implantation genetic diagnosis; single cell gel electrophoresis; single nucleotide variations; the Human Gene Mutation Database; whole exome sequencing.