Open AccessHPDL mutations identified by exome sequencing are associated with infant neurodevelopmental disorders
Author(s) -
Wang Yanhong,
Zheng Xuan,
Feng Chao,
Fan Xiaoge,
Liu Lei,
Guo Pengbo,
Lei Zhi,
Mei Shiyue
Publication year - 2022
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.2025
Subject(s) - exome sequencing , neurodevelopmental disorder , medicine , corpus callosum , proband , spasticity , sanger sequencing , ventriculomegaly , microcephaly , polymicrogyria , autism spectrum disorder , pediatrics , magnetic resonance imaging , pathology , autism , phenotype , genetics , mutation , biology , physical medicine and rehabilitation , psychiatry , pregnancy , gene , radiology , fetus
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.