Monash Genetics, Monash Health, Melbourne, VIC, Australia.
Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
BMC Med Genomics. 2024 Aug 5;17(1):195. doi: 10.1186/s12920-024-01945-0.
The Cut Homeobox 1 (CUX1) gene has been implicated in a number of developmental processes and has recently emerged as an important cause of developmental delay and impaired intellectual development. Individuals with variants in CUX1 have been described with a variety of co-morbidities including variations in sex development (VSD) although these features have not been closely documented.
The proband is a 14-year-old male who presented with congenital complex hypospadias, neurodevelopmental differences, and subtle dysmorphism. A family history of neurodevelopmental differences and VSD was noted. Microarray testing and whole exome sequencing found the 46,XY proband had a large heterozygous in-frame deletion of exons 4-10 of the CUX1 gene.
Our review of the literature has revealed that variants in CUX1 are associated with a range of VSD and suggest this gene should be considered in cases where a VSD is noted at birth, especially if there is a familial history of VSD and/or neurodevelopmental differences. Further work is required to fully investigate the role and regulation of CUX1 in sex development.
Cut 同源盒 1（CUX1）基因参与了许多发育过程，最近它已成为发育迟缓及智力发育受损的一个重要原因。携带 CUX1 变异的个体表现出多种共患病，包括性别发育变异（VSD），尽管这些特征尚未得到密切记录。
先证者是一名 14 岁男性，表现为先天性复杂型尿道下裂、神经发育差异和轻微的发育不良。家族史中有神经发育差异和 VSD 的记录。微阵列测试和全外显子测序发现，46，XY 先证者 CUX1 基因的外显子 4-10 存在一个大的杂合框内缺失。
我们对文献的回顾表明，CUX1 变异与一系列 VSD 相关，并提示在出生时发现 VSD 的情况下，应考虑该基因，特别是如果存在 VSD 和/或神经发育差异的家族史。需要进一步的研究来全面研究 CUX1 在性别发育中的作用和调节。
