Clustered structural variants involving PHEX at Xp22 in a female patient with X-linked hypophosphatemia.

IF 1.7 4区生物学 Q4 CELL BIOLOGY

Cytogenetic and Genome Research Pub Date : 2025-07-02 DOI:10.1159/000547186

Erika Uehara, Yasuhiro Naiki, Atsushi Hattori, Maki Fukami, Keiko Matsubara

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引用次数: 0

Abstract

Introduction: X chromosomal structural changes involving PHEX result in X-linked hypophosphatemia (XLH). However, their underlying mechanisms were poorly determined. Moreover, X chromosome inactivation (XCI) statuses in female patients with XLH remain to be studied.

Case presentation: We conducted systematic genomic analyses for a woman with XLH and detected a 3.2 Mb tandem duplication at Xp22.33, a 1.9 Mb tandem duplication at Xp22.31, and a 0.8 Mb deletion involving PHEX at Xp22.11 on the paternally derived chromosome. The fusion junctions contained templated insertions and short nucleotide additions indicative of non-homologous end joining (NHEJ) or alternative-NHEJ. The patient had random XCI.

Conclusion: This study provides evidence that PHEX haploinsufficiency leads to typical XLH in women with random XCI and that a 5.9 Mb rearrangement on Xp22 permits random XCI. Our results, together with previous findings, imply that clustered structural changes due to NHEJ/alternative-NHEJ are a unique type of human genomic rearrangements.

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1例x连锁低磷血症女性患者Xp22处涉及PHEX的聚集性结构变异

简介：涉及PHEX的X染色体结构改变导致X连锁低磷血症（XLH）。然而，它们的潜在机制尚不清楚。此外，女性XLH患者的X染色体失活（XCI）状况仍有待研究。病例介绍：我们对一名患有XLH的女性进行了系统的基因组分析，在父系来源的染色体上检测到Xp22.33处3.2 Mb的串联重复，Xp22.31处1.9 Mb的串联重复和Xp22.11处涉及PHEX的0.8 Mb缺失。融合连接包含模板插入和短核苷酸添加，表明非同源末端连接（NHEJ）或替代NHEJ。患者随机发生XCI。结论：本研究提供了证据，证明PHEX单倍体功能不全导致随机XCI女性的典型XLH，并且Xp22上5.9 Mb的重排允许随机XCI。我们的研究结果与之前的研究结果一起表明，由于NHEJ/替代-NHEJ导致的集群结构变化是一种独特的人类基因组重排类型。

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

Cytogenetic and Genome Research 生物-细胞生物学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

1 months

期刊介绍： During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.