HPDL mutations identified by exome sequencing are associated with infant neurodevelopmental disorders

Abstract

Background Recent research found that biallelic HPDL variants can cause neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), with only a few reports. Clinical phenotypic information on individuals with damaging HPDL variants may also be incomplete. The phenotype of NEDSWMA is characterized by severe neurodevelopmental delay, brain atrophy, and spasticity in infancy. Methods Exome sequencing was used in the proband and his parents to identify the underlying genetic cause. Candidate mutations were validated by classic Sanger sequencing. The clinical presentation of the infant who carried HPDL variants was summarized. Results We identified a novel compound heterozygous variants in HPDL, c.995delC (p.T332Mfs) and c.1051C>T (p.Q351*) in the patient a 6‐month‐old boy presenting with global developmental delay, seizures, hypertonia, and limb spasticity. Brain magnetic resonance imaging (MRI) showed thin corpus callosum, ventriculomegaly, white matter volume reduction, bilateral frontotemporal subarachnoid widening, and sulcus deeping. Conclusion Our results provided important information for the associations of variants in HPDL with the neurodevelopmental disorder in infants, and broaden the genetic spectrum of HPDL‐related disease. This is the second report of the HPDL mutation causing infant neurodevelopmental disorders in a Chinese population.

Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders

“…Clinically the boy presented with developmental delay, seizures and spasticity. Brain MRI revealed a thin corpus callosum, ventriculomegaly and white matter volume reduction [ 63 ].…”

Primary Coenzyme Q10 Deficiency: An Update

“…Whilst not part of the COQ1–COQ10 gene mutation series described above, the enzyme 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) has also been shown to have a role in CoQ10 biosynthesis [ 99 ]. Patients with HPDL deficiency have been reported by Husain et al (17 individuals, [ 100 ]), Wiessner et al (34 individuals, [ 101 ]), Wang et al (1 individual, [ 102 ]), and Micule et al (2 individuals, [ 103 ]). The patient ages in these studies ranged from 6 months to 39 years; the clinical presentation typically included development delay, seizures, and spasticity.…”