A 42-year-old woman with 4H leukodystrophy caused by a homozygous mutation in POLR3A gene

作者：Yiming Yang, Zhong-Min Zhao, Yanli Jia, Yangjuan Jia, Ning Han, Jianhua Wang · 发表于：Chinese Medical Journal · 年份：2019 · DOI：10.1097/cm9.0000000000000328 · 被引用次数：10 · 研究领域：RNA regulation and disease、Fluoride Effects and Removal

To the Editor: Leukodystrophies are a heterogeneous group of inherited neurological disorders characterized by impairing myelin of the white matter. Based on the original definition of the leukodystrophy, Timmons et al[1] described four patients with hypomyelination, hypogonadotropic hypogonadism, and hypodontia, and proposed naming this disease as 4H syndrome. Several years later, it was identified that mutations in POLR3A or POLR3B genes, encoding for the two largest sub-units of the RNA polymerase III, were shown to cause 4H leukodystrophy.[2] We here report a woman with 4H leukodystrophy carried the c.1911+18 C>T mutation in POLR3A in a homozygous state, which is the first report with this mutation site in China. A 42-year-old woman, born to non-consanguineous parents with no family history of neurological diseases, suffered from ataxia for 3 years. After a normal psychomotor development, the patient first presented dental eruption at 1-year-old and with absence at 5 years of age. She stopped growing when she was 15 years old, and remained heights under 150 cm. Intellectual impairment became evident at 35 years old. Approximately 4 years ago (38 years old), she appeared secondary amenorrhea. Ataxia aggravated in the following 3 years and gradually affected daily life. On examinations, she has short stature [Supplementary Figure 1], tooth dysplasia and ataxia-related syndrome. There were no nystagmus, papilla atrophy or other visual problems. Her Mini-Mental State Examinat...