Whole genome sequencing followed by functional analysis of genomic deletion encompassing ERCC8 and NDUFAF2 genes in a non-consanguineous Indian family reveals dysfunctional mitochondrial bioenergetics leading to infant mortality.

• In a patient with mitochondrial disorder, compound heterozygous deletion with an overlapping region of ∼142 kb encompassing NDUFAF2 and ERCC8 genes was identified. • Mitochondrial dysfunction was observed in fetal-derived fibroblasts harboring the contiguous gene deletion. • Custom MLPA-based assay was developed to screen the identified deletion in the extended family of the proband. Genomic investigations on an infant who presented with a putative mitochondrial disorder led to identification of compound heterozygous deletion with an overlapping region of ∼142 kb encompassing two nuclear encoded genes namely ERCC8 and NDUFAF2. Investigations on fetal-derived fibroblast culture demonstrated impaired bioenergetics and mitochondrial dysfunction, which explains the phenotype and observed infant mortality in the present study. The genetic findings from this study extended the utility of whole-genome sequencing as it led to development of a MLPA-based assay for carrier screening in the extended family and the prenatal testing aiding in the birth of two healthy children. [ABSTRACT FROM AUTHOR]