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Abstract：
Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a rare disorder of unknown etiology. It has been proposed to be autosomal-recessive and is characterized by variable clinical features, such as intrauterine growth restriction and poor postnatal weight gain, characteristic facial features (triangular appearance to the face, convex nasal profile or pinched nose, and small mouth), widened fontanelles, pseudohydrocephalus, prominent scalp veins, lipodystrophy, and teeth abnormalities. A previous report described a single WRS patient with bi-allelic truncating and splicing variants in POLR3A. Here we present seven additional infants, children, and adults with WRS and bi-allelic truncating and/or splicing variants in POLR3A. POLR3A, the largest subunit of RNA polymerase III, is a DNA-directed RNA polymerase that transcribes many small noncoding RNAs that regulate transcription, RNA processing, and translation. Bi-allelic missense variants in POLR3A have been associated with phenotypes distinct from WRS: hypogonadotropic hypogonadism and hypomyelinating leukodystrophy with or without oligodontia. Our findings confirm the association of bi-allelic POLR3A variants with WRS, expand the clinical phenotype of WRS, and suggest specific POLR3A genotypes associated with WRS and hypomyelinating leukodystrophy.
摘要：
Wiedemann-Rautenstauch综合征（WRS），也被称为新生儿孕激素综合征，是一种病因不明的罕见疾病。它已被认为是常染色体隐性遗传，并以可变的临床特征为特征，如宫内生长受限和出生后体重增加不良，特征性面部特征(面部三角形外观，鼻凸轮廓或捏住鼻子，和小嘴巴)，加宽的fontanelles，假性脑积水,突出的头皮静脉，脂肪营养不良,牙齿异常先前的报告描述了在POLR3A中具有双等位基因截短和剪接变体的单个WRS患者。这里我们介绍了另外七个婴儿，孩子们,和在POLR3A中具有WRS和双等位基因截短和/或剪接变体的成年人。POLR3A,RNA聚合酶III的最大亚基，是一种DNA指导的RNA聚合酶，它转录许多调节转录的小的非编码RNA，RNA加工，和翻译。POLR3A中的双等位基因错义变体与不同于WRS的表型相关：低促性腺激素性性腺机能减退和伴有或不伴有少核的骨髓增生性脑白质营养不良。我们的发现证实了双等位基因POLR3A变体与WRS的关联，扩大WRS的临床表型，并提示特定的POLR3A基因型与WRS和髓鞘性脑白质营养不良相关。
