RESUMO
BACKGROUND: ECEL1 has been presented as a causal gene of an autosomal recessive form distal arthrogryposis (DA) which affects the distal joints. The present study focused on bioinformatic analysis of a novel mutation in ECEL1, c.535A>G (p. Lys179Glu), which was reported in a family with 2 affected boys and fetus through prenatal diagnosis. METHODS: Whole-exome sequencing data analyzed followed by molecular dynamic (MD) simulation of native ECEL1 protein and mutant structures using GROMACS software. One variant c.535A>G, p. Lys179Glu (homozygous) on gene ECEL1 has been detected in proband which was validated in all family members through Sanger sequencing. RESULTS: We demonstrated remarkable constructional differences by MD simulation between wild-type and novel mutant of ECEL1 gene. The reason for the lack of the Zn ion binding in mutation in the ECEL1 protein has been identified by average atomic distance and SMD analysis among the wild-type and mutant. CONCLUSION: Overall, in this study, we present knowledge of the effect of the studied variant on the ECEL1 protein leading to neurodegenerative disorder in humans. This work may hopefully be supplementary to classical molecular dynamics to dissolve the mutational effects of cofactor-dependent protein.
