Whole exome sequencing identifies a rare variant in DAAM2 as a potential candidate in idiopathic pulmonary ossification.

Abstract

Background\nDiffuse pulmonary ossification (DPO) is a rare disease characterized by bone tissue formation in the lung. DPO can be classified into idiopathic pulmonary ossification (IPO) and secondary pulmonary ossification. Cases with no identified etiology are classified as IPO. Variants of dishevelled associated activator of morphogenesis 2 (DAAM2) have been reported to be involved in the bone-resorption of osteoclasts.\n\n\nMethods\nWhole exome sequencing (WES) was used on samples from a patient with IPO and his healthy parents. The effects of all variants were determined using functional predictors (PolyPhen-2, SIFT, FATHMM and MutationTaster); variants existing only in the patient were further screened compared with his healthy parents.\n\n\nResults\nForty deleterious variants, including 25 single nucleotide variants (SNVs) and 15 insertions and deletions (indels), were identified by WES. Finally, DAAM2 (c.G2960T:p.R987L) was screened by pathway analysis.\n\n\nConclusions\nWe identified a novel variant of DAAM2 (c.G2960T:p.R987L) that might participate in the disease process of IPO.