Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Henan Children's Hospital, Zhengzhou Children's Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Department of Rehabilitation Medicine, Henan Children's Hospital, Zhengzhou Children's Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Mol Genet Genomic Med. 2022 Oct;10(10):e2025. doi: 10.1002/mgg3.2025. Epub 2022 Aug 19.
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.
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.
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.
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.
最近的研究发现，双等位基因 HPDL 变异可导致伴有进行性痉挛和脑白质异常的神经发育障碍（NEDSWMA），仅有少数报道。具有破坏性 HPDL 变异的个体的临床表型信息也可能不完整。NEDSWMA 的表型特征为严重的神经发育迟缓、脑萎缩和婴儿期痉挛。
对先证者及其父母进行外显子组测序，以确定潜在的遗传原因。通过经典 Sanger 测序验证候选突变。总结携带 HPDL 变异的婴儿的临床表现。
我们在一名 6 个月大的男孩中发现了 HPDL 的一种新的复合杂合变异，c.995delC（p.T332Mfs）和 c.1051C>T（p.Q351*），该男孩表现为全面发育迟缓、癫痫发作、高肌张力和四肢痉挛。脑磁共振成像（MRI）显示胼胝体变薄、脑室扩大、脑白质体积减少、双侧额颞部蛛网膜下腔增宽和脑沟加深。
我们的结果为 HPDL 变异与婴儿神经发育障碍的相关性提供了重要信息，并扩展了 HPDL 相关疾病的遗传谱。这是 HPDL 突变导致中国人群婴儿神经发育障碍的第二例报道。
