Genetic analysis of an asymptomatic female with a large Xp deletion revealed insights into the X chromosome inactivation pattern: a case report.

IF 1.4 4区生物学 Q4 GENETICS & HEREDITY

Molecular Cytogenetics Pub Date : 2025-09-30 DOI:10.1186/s13039-025-00729-0

Li-Jun Zhang, Wen-Lan Liu, Shu-Yi Shao, Yong Xu, Lu Zhou

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引用次数: 0

Abstract

Background: X-linked disorders caused by skewed X chromosome inactivation (XCI) result in phenotypic heterogeneity, which is rarely reported. XCI testing is not widely used in clinical cases, making risk assessment for carriers of X-linked unbalanced structural abnormalities challenging.

Case presentation: We present genetic data from an asymptomatic female with a de novo 6.31 Mb deletion on Xp11.23-p11.22, identified through CMA-array analysis. The deletion includes 101 OMIM genes, 11 haplo-insufficient (HI) genes, and 4 escape genes. An androgen receptor (AR) methylation assay showed a 100% skewed XCI pattern silencing the abnormal X-chromosome. RNA-seq analysis revealed up-regulation of escape genes within the deletion at the transcriptional level. The absence of a severe clinical phenotype, aside from infertility, in this female was most likely attributed to the extremely skewed XCI and the compensatory up-regulation of XCI escape genes.

Conclusions: Our data indicate that XCI can modify the phenotype in female carriers of heterozygous X-linked deletion and provide valuable information about the analysis of XCI pattern in risk assessment of this kind cases, especially precious fetuses.

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对一个无症状女性的大量Xp缺失的遗传分析揭示了对X染色体失活模式的见解：一个病例报告。

背景：斜X染色体失活（XCI）引起的X连锁疾病导致表型异质性，很少有报道。XCI检测并未广泛应用于临床病例，这使得对x连锁不平衡结构异常携带者的风险评估具有挑战性。病例介绍：我们报告了一名无症状女性的遗传数据，该女性在Xp11.23-p11.22上从头缺失6.31 Mb，通过cma阵列分析确定。缺失包括101个OMIM基因、11个单倍体缺陷基因和4个逃逸基因。雄激素受体（AR）甲基化试验显示100%偏斜XCI模式沉默异常x染色体。RNA-seq分析显示，在转录水平上，缺失中的逃逸基因上调。除了不孕之外，这名女性没有严重的临床表型，很可能是由于XCI极度偏斜和XCI逃逸基因的补偿性上调。结论：我们的数据表明XCI可以改变杂合x连锁缺失女性携带者的表型，为分析XCI模式对这类病例特别是珍贵胎儿的风险评估提供了有价值的信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cytogenetics GENETICS & HEREDITY-

CiteScore

2.60

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Cytogenetics encompasses all aspects of chromosome biology and the application of molecular cytogenetic techniques in all areas of biology and medicine, including structural and functional organization of the chromosome and nucleus, genome variation, expression and evolution, chromosome abnormalities and genomic variations in medical genetics and tumor genetics. Molecular Cytogenetics primarily defines a large set of the techniques that operate either with the entire genome or with specific targeted DNA sequences. Topical areas include, but are not limited to: -Structural and functional organization of chromosome and nucleus- Genome variation, expression and evolution- Animal and plant molecular cytogenetics and genomics- Chromosome abnormalities and genomic variations in clinical genetics- Applications in preimplantation, pre- and post-natal diagnosis- Applications in the central nervous system, cancer and haematology research- Previously unreported applications of molecular cytogenetic techniques- Development of new techniques or significant enhancements to established techniques. This journal is a source for numerous scientists all over the world, who wish to improve or introduce molecular cytogenetic techniques into their practice.