背景:POLR3相关的脑白质营养不良是一组罕见的神经退行性疾病,其特征是白质变性,具有不同的主要临床特征组合。
方法:一名18岁的女士因从小没有月经而入院。她逐渐出现轻微症状,例如在过去的两年里喝水后窒息和行走不稳定。此外,她的考试成绩和反应能力远低于同龄人。体格检查显示她的身材有点矮,表现僵硬,双侧乳房增大。她在检查共济失调时表现出笨拙的动作,SARA得9分.
结果:实验室数据显示雌二醇水平降低,FSH,LH,MoCA得分为7分。常规核型分析显示46XX9qh核型。超声提示原子宫(19×11×10mm)。头颅MRI显示双侧大脑半球髓鞘发育不良,脑萎缩,薄的call体,和小脑垂体,有不均匀的强化和扩大的脑室。外显子组测序显示POLR3A基因有两个错义突变(c.3013C>T和c.1757C>T),从她的母亲和父亲那里继承下来,分别。
结论:总的来说,我们确定了POLR3A基因的新复合杂合突变,该突变导致患者的POLR3A相关的无髓鞘性脑白质营养不良伴性腺功能减退,并结合临床表现,MRI大脑模式,和医学外显子组测序。
结论:临床表型的复杂性和基因型的异质性在基因诊断中提出了新的挑战。这项研究将进一步帮助我们了解POLR3A相关的脑白质营养不良,并促进进一步分析相关疾病的表型-基因型相关性。
BACKGROUND: POLR3-related leukodystrophy is a group of rare neurodegenerative disorders characterized by degeneration of the white matter with different combinations of major clinical features.
METHODS: An 18-year-old lady was admitted for no menstruation since childhood. She gradually developed slight symptoms, such as choking after drinking water and unsteady walking in the last 2 years. Furthermore, her test scores and response capability were far lower than that of her peers. Physical examination revealed her to be of a slightly short stature, with stiff expressions and bilateral breast enlargement. She revealed clumsy movements when examined for ataxia, with an SARA score of 9.
RESULTS: The laboratory data revealed a decreased level of estradiol, FSH, and LH, with a MoCA score of 7. Conventional karyotype analysis revealed a 46 XX 9qh + karyotype. Ultrasound indicated primordial uterus (19 × 11 × 10 mm). Brain MRI showed bilateral cerebral hemisphere myelin dysplasia, brain atrophy, thin corpus callosum, and small pituitary gland with uneven reinforcement and enlarged ventricles. Exome sequencing exhibited two missense mutations in the
POLR3A gene (c.3013C > T and c.1757C > T), which were inherited from her mother and father, respectively.
CONCLUSIONS: Collectively, we identified novel compound heterozygous mutations of the
POLR3A gene that caused
POLR3A-related hypomyelinating leukodystrophy with hypogonadism in the patient combined with the clinical presentation, MRI brain pattern, and medical exome sequencing.
CONCLUSIONS: The complexity of clinical phenotypes and heterogeneity of genotypes raise new challenges in genetic diagnoses. This study will further aid our understanding of
POLR3A-related leukodystrophy and promote further analysis of phenotype-genotype correlations of related diseases.