First Identification of a Heterozygous RNU4-2 and RNU4-1 Deletion Associated With Fetal Urogenital and Anorectal Malformations

首次发现与胎儿泌尿生殖系统和肛门直肠畸形相关的RNU4-2和RNU4-1杂合缺失

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Abstract

What is already known about this topic? ◦. Pathogenic sequence variants in RNU4‐2 cause ReNU syndrome characterized by severe neurodevelopmental disorder, microcephaly, and brain malformations. ◦. This syndrome has been recently described in hundreds of individuals. Urogenital malformations have not been described as part of the ReNU syndrome spectrum. What does this study add? ◦. We report the first identification of a complete deletion encompassing RNU4‐2/RNU4‐1 genes, presenting with bilateral renal and bladder agenesis, anorectal atresia, and vertebral anomalies resembling VATER/VACTERL association. ◦. This case suggests U4 snRNA haploinsufficiency as a candidate mechanistic hypothesis for these anomalies, which are markedly distinct from the phenotype associated with pathogenic sequence variants in RNU4‐2.

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