DNAJC12-associated developmental delay, movement disorder, and mild hyperphenylalaninemia identified by whole-exome sequencing re-analysis. (December 2018)

• Record Type: Journal Article
• Authors: Veenma, Danielle; Cordeiro, Dawn; Sondheimer, Neal; Mercimek-Andrews, Saadet
• Is Part Of: European journal of human genetics. Volume 26:Number 12(2018)
• Page Start: 1867
• Page End: 1870
• Publication Date: 2018-12
• Subjects: Human genetics -- Periodicals; Medical genetics -- Periodicals; 616.042
• DOI: 10.1038/s41431-018-0237-9
• Languages: English
• ISSNs: 1018-4813

Abstract

Abstract Hyperphenylalaninemia, movement disorder, and intellectual disability due to variants inDNAJC12 is a recently reported inherited neurotransmitter disorder. We report two new patients with this new genetic disorder. Patient 1 is a 6-year-11-month-old boy with mild hyperphenylalaninemia and global developmental delay (GDD). Seventeen-year-old male sibling of patient 1 had GDD from the first year of life. He had mild hyperphenylalaninemia at 11.5 years of age following his younger brother's diagnosis. He had low levels of homovanillic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid. Whole-exome sequencing (WES) was normal in 2016. After the first description ofDNAJC12 -associated hyperphenylalaninemia, dystonia, and intellectual disability in 2017, WES re-analysis identified a homozygous c.58_59delGG (p.(Gly20Metfs*2)) variant inDNAJC12 . His younger brother was homozygous for the same variant, confirming the diagnosis ofDNAJC12 -associated hyperphenylalaninemia, movement disorder, and intellectual disability. Mild hyperphenylalaninemia and GDD should warrant targetedDNAJC12 genetic testing for the early diagnosis ofDNAJC12- associated hyperphenylalaninemia, movement disorder, and intellectual disability.