Polymelia Treatment, Whole-Exome Sequencing and Disease Network Analysis

Abstract

Background: Polymelia is a rare congenital disease that is mainly characterized by extra limbs, and the mechanism of this rare congenital malformation in humans is still unclear. Methods: DNA was isolated from peripheral blood mononuclear cells from one child with three lower extremities accompanied by congenital malformations and his parents for whole-exome sequencing. We performed operations to simultaneously truncate the lower limb and repair the abdominal wall hernia. Findings: 29 mutated genes were identified in the proband using three hypothetical inheritance patterns (Recessive model, X-linked model and de novo mutation model). Using an Ingenuity Pathway Analysis (IPA), the disease network analysis demonstrated that the network of Cancer, Connective Tissue Disorders, Organismal Injury and Abnormalities included eleven mutated genes that might play roles in the child's multi-malformations. The possible variants of three collagen-associated genes, including rs146977141 c.5168 A > G (p.N1723S) and rs372335521 c.5207 C > T (p.T1736M) in COL27A1, c.1786_1794del (p.596_598del) and c.2106_2114del (p.702_705del) in COL18A1 and rs754836509 c.3940 C > T (p.P1314S) in COL4A5, were further validated in the proband by Sanger sequencing and an alignment analysis. Interpretation: The variants of the three collagen-associated genes may be critical for the child's multi-malformations. Funding: National Natural Science Foundation of China and Shen Kang Hospital Development Center Foundation. Declaration of Interest: The authors have no competing interests to declare. Ethical Approval: This study was approved by the Shanghai Public Health Clinical Center Institutional Review Board, and written informed consent was obtained from the parents of the proband.