PDF(Pubmed)
Abstract：
Background: Infantile hypotonia with psychomotor retardation and characteristic facies 2 (IHPRF2) is a rare autosomal recessive neurodevelopmental disorder caused by mutations in the UNC80 gene. It is characterized by severe global developmental delay, poor or absent speech and absent or limited walking abilities. The current study explored a case of a Chinese patient with IHPRF2 caused by a novel splicing variant of UNC80. Case Report: The proband is a 8-year-old Chinese male manifested with global developmental delay, severe truncal hypotonia, absent speech and intellectual disability. SNP array analysis revealed a uniparental isodisomy of the entire chromosome 2 [UPD(2)] in the proband. Whole exome sequencing (WES) subsequently identified a novel mutation c.5609-4G>A in the UNC80 gene, which was inherited from his mother and was confirmed by Sanger sequencing, indicating that UPD(2) was of maternal origin. Conclusion: A novel UNC80 homozygous splicing variant c.5609-4G>A associated with maternal UPD(2) was identified. These findings indicate that UPD poses a high risk of autosomal recessive diseases, and provides information on the variant spectrum for UNC80. Our findings elucidate on understanding of the genotype-phenotype associations that occur in IHPRF2 patients.
摘要：
背景：伴有精神运动发育迟缓和特征性相2（IHPRF2）的婴儿张力低下是一种罕见的常染色体隐性遗传神经发育障碍，由UNC80基因突变引起。它的特点是全球严重的发育迟缓，不良或无言语，行走能力缺失或有限。当前的研究探索了一例由UNC80的新型剪接变体引起的IHPRF2中国患者。病例报告：先证者是一名8岁的中国男性，表现为全球发育迟缓，严重的躯干肌张力减退,缺乏言语和智力残疾。SNP阵列分析揭示了先证者中整个2号染色体[UPD（2）]的单亲等异体性。全外显子组测序（WES）随后在UNC80基因中鉴定出一个新的突变c.5609-4G>A，这是从他母亲那里继承的，并得到了桑格测序的证实，表明UPD（2）是母体来源的。结论:鉴定了与母体UPD(2)相关的新型UNC80纯合剪接变体c.5609-4G>A。这些发现表明UPD构成常染色体隐性遗传疾病的高风险，并提供了UNC80变异谱的信息。我们的发现阐明了对IHPRF2患者中发生的基因型-表型关联的理解。
