Utilization of targeted array comparative genomic hybridization, MitoMet, in prenatal diagnosis of metabolic...

Metabolic disorders are inborn errors that often present in the neonatal period with a devastating clinical course. If not treated promptly, these diseases can result in severe, irreversible disease or death. Determining the molecular defects in metabolic diseases is important in providing a definitive diagnosis for patient management. Therefore, prenatal diagnosis for families with known mutations causing metabolic disorders is crucial for timely intervention. Here we present three families in which standard Sanger sequencing failed to provide a definitive diagnosis, but the detection of genomic deletions by array comparative genomic hybridization (CGH) specifically targeted to mitochondrial and metabolic disease genes, MitoMet®, was fundamental in providing accurate prenatal diagnosis. In addition, to our knowledge, two deletions are the smallest detected by oligonucleotide array CGH reported for their respective genes, OTC and ARG1. These data highlight the importance of targeted array CGH in patients with suspected metabolic disorders and incomplete or negative sequencing results, as well as its emerging role in prenatal diagnosis.