Novel mutations of POLR3A Gene caused hypomyelinating leukodystrophy type 7 (HLD7) in a Chinese family: a Case Report

Abstract Background Hypomyelinating leukodystrophy 7 (HLD7) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline that manifests as spasticity, ataxia, tremor, and cerebellar symptoms, as well as mild cognitive regression and hypodontia. HLD7 belongs to the family of RNA polymerase III-related leukodystrophy, which are caused by biallelic mutations in the POLR3A or POLR3B gene. Case presentation In this study, we report a female child with HLD7 manifesting as cognitive decline, moderate dysarthria, intellectual disability, cerebellar syndrome, short stature, dysphagia, hypodontia, and aberrant brain imaging. Interestingly, polytrichia and bronchodysplasia were first observed in the HLD7 patient. Medical exome sequencing with high coverage depth was employed to identify potential genetic variants in the patient. Novel compound heterozygous mutations of the POLR3A gene, c.1771-6C>G and c.2611del (p.M871Cfs*8), were detected. One of them is an uncommon splice site mutation, and this is the first report of this mutation in a Chinese family. The father was determined to be a heterozygous carrier of the c.2611del (p.M871Cfs*8) mutation and the mother a heterozygous carrier of the c.1771-6C>G mutation. Conclusion The patient’s newly emerged clinical features and mutations provide useful information for further exploration of genotype-phenotype correlations of HLD7.