PDF(Pubmed)
Abstract：
BACKGROUND: Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive neonatal progeroid disorder characterized by prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, and mental impairment.
METHODS: A 6-year-old patient, who initially presented with multiple postnatal abnormalities, facial dysplasia, micrognathia, skull appearance, hallux valgus, and congenital dislocation of the hip, was recruited in this study. The patient was initially diagnosed with progeria. The mother of the patient had abnormal fetal development during her second pregnancy check-up, and the clinical phenotype of the fetus was similar to that of the patient. Whole-exome sequencing (WES) of the patient was performed, and POLR3B compound heterozygous variants-c.2191G > C:p.E731Q and c.3046G > A:p.V1016M-were identified in the patient. Using Sanger sequencing, we found that the phenotypes and genotypes were segregated within the pedigree. These two variants are novel and not found in the gnomAD and 1000 Genomes databases. The two mutation sites are highly conserved between humans and zebrafish.
CONCLUSIONS: Our study not only identified a novel WRS-associated gene, POLR3B, but also broadened the mutational and phenotypic spectra of POLR3B. Furthermore, WES may be useful for identifying rare disease-related genetic variants.
METHODS: A 6-year-old patient, who initially presented with multiple postnatal abnormalities, facial dysplasia, micrognathia, skull appearance, hallux valgus, and congenital dislocation of the hip, was recruited in this study. The patient was initially diagnosed with progeria. The mother of the patient had abnormal fetal development during her second pregnancy check-up, and the clinical phenotype of the fetus was similar to that of the patient. Whole-exome sequencing (WES) of the patient was performed, and POLR3B compound heterozygous variants-c.2191G > C:p.E731Q and c.3046G > A:p.V1016M-were identified in the patient. Using Sanger sequencing, we found that the phenotypes and genotypes were segregated within the pedigree. These two variants are novel and not found in the gnomAD and 1000 Genomes databases. The two mutation sites are highly conserved between humans and zebrafish.
CONCLUSIONS: Our study not only identified a novel WRS-associated gene, POLR3B, but also broadened the mutational and phenotypic spectra of POLR3B. Furthermore, WES may be useful for identifying rare disease-related genetic variants.
摘要：
背景：Wiedemann-Rautenstrauch综合征（WRS）是一种罕见的常染色体隐性遗传新生儿孕激素疾病，其特征是产前和产后生长迟缓，身材矮小,早衰的外观，低张力,和精神损害。
方法：一名6岁的患者，最初出现多种产后异常，面部发育不良,小颌畸形,头骨外观,外翻,先天性髋关节脱位，在这项研究中被招募。患者最初被诊断患有早衰症。病人的母亲在第二次怀孕检查时胎儿发育异常,胎儿的临床表型与患者相似。对患者进行全外显子组测序（WES），和POLR3B复合杂合变体-c.2191G>C:p.E731Q和c.3046G>A：p。在患者中鉴定出V1016M。使用Sanger测序,我们发现表型和基因型在谱系中是分开的。这两种变体是新颖的,并且在gnomAD和1000基因组数据库中未发现。这两个突变位点在人类和斑马鱼之间高度保守。
结论：我们的研究不仅发现了一个新的WRS相关基因，POLR3B,而且还扩大了POLR3B的突变和表型谱。此外，WES可用于鉴定罕见的疾病相关遗传变异。
方法：一名6岁的患者，最初出现多种产后异常，面部发育不良,小颌畸形,头骨外观,外翻,先天性髋关节脱位，在这项研究中被招募。患者最初被诊断患有早衰症。病人的母亲在第二次怀孕检查时胎儿发育异常,胎儿的临床表型与患者相似。对患者进行全外显子组测序（WES），和POLR3B复合杂合变体-c.2191G>C:p.E731Q和c.3046G>A：p。在患者中鉴定出V1016M。使用Sanger测序,我们发现表型和基因型在谱系中是分开的。这两种变体是新颖的,并且在gnomAD和1000基因组数据库中未发现。这两个突变位点在人类和斑马鱼之间高度保守。
结论：我们的研究不仅发现了一个新的WRS相关基因，POLR3B,而且还扩大了POLR3B的突变和表型谱。此外，WES可用于鉴定罕见的疾病相关遗传变异。
