Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 36, Lebanon.
Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 36, Lebanon.
Genes (Basel). 2024 Jul 10;15(7):901. doi: 10.3390/genes15070901.
Duplications on the short arm of chromosome X, including the gene , have been associated with gonadal dysgenesis and with male to female sex reversal. Additional clinical manifestations can be observed in the affected patients, depending on the duplicated genomic region. Here we report one of the largest duplications on chromosome X, in a Lebanese patient, and we provide the first comprehensive review of duplications in this genomic region.
A 2-year-old female patient born to non-consanguineous Lebanese parents, with a family history of one miscarriage, is included in this study. The patient presents with sex reversal, dysmorphic features, optic atrophy, epilepsy, psychomotor and neurodevelopmental delay. Single nucleotide variants and copy number variants analysis were carried out on the patient through exome sequencing (ES). This showed an increased coverage of a genomic region of around 23.6 Mb on chromosome Xp22.31-p21.2 (g.7137718-30739112) in the patient, suggestive of a large duplication encompassing more than 60 genes, including the gene involved in sex reversal. A karyotype analysis confirmed sex reversal in the proband presenting with the duplication, and revealed a balanced translocation between the short arms of chromosomes X and 14:46, X, t(X;14) (p11;p11) in her/his mother.
This case highlights the added value of CNV analysis from ES data in the genetic diagnosis of patients. It also underscores the challenges encountered in announcing unsolicited incidental findings to the family.
X 染色体短臂上的重复，包括 基因，与性腺发育不全和男性到女性的性别反转有关。受影响的患者可能会出现其他临床表现，具体取决于重复的基因组区域。在这里，我们报告了一个在黎巴嫩患者中发现的 X 染色体上最大的重复之一，并对该基因组区域的重复进行了首次全面综述。
一名 2 岁的女性患者，出生于非近亲黎巴嫩父母，有一次流产史，纳入本研究。该患者表现为性别反转、畸形特征、视神经萎缩、癫痫、精神运动和神经发育迟缓。通过外显子组测序（ES）对患者进行单核苷酸变异和拷贝数变异分析。结果显示，患者 Xp22.31-p21.2 （g.7137718-30739112）染色体上的一个基因组区域的覆盖度增加，约为 23.6 Mb，提示存在一个包含 60 多个基因的大片段重复，包括涉及性别反转的 基因。核型分析证实了先证者的性别反转，并显示其母亲的 X 染色体和 14 号染色体短臂之间存在平衡易位：46，X，t(X;14)（p11;p11）。
本病例突出了 ES 数据中的 CNV 分析在患者遗传诊断中的附加价值。它还强调了向家庭公布意外的偶然发现所面临的挑战。
