Two novel mutations in DNAJC12 identified by whole-exome sequencing in a patient with mild hyperphenylalaninemia

Recently hyperphenylalaninemia (HPA) caused by variants in DNAJC12 was reported and this suggested a new strategy for diagnosis. But DNAJC12-associated HPA is a rare in Chinese population so far.

The clinical information and blood samples from the patient and his family members were collected and analyzed. Whole-exome sequencing (WES) was used to identify the causative gene.

We reported a newborn patient with HPA, having excluded the causes in common genes associated with HPA. By using whole-exome sequencing, novel compound heterozygosity mutations in DNAJC12 were found, namely c.306C>G (p.His102Gln) and c.182delA (p.Lys61Argfs*6). Administering a diet with low phenylalanine combined with tetrahydrobiopterin and neurotransmitter precursors were shown to be effective in preventing neurodevelopmental delay for these patients.

Our finding confirms the diagnosis of DNAJC12-associated HPA and suggests that genetic detection of DNAJC12 should be considered when newborn screening results are positive for HPA.