Complex genomic rearrangement with deletion of PITX2 in a Chinese family with Axenfeld-Rieger syndrome: A case report and literature review.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Vision Pub Date : 2024-12-31 eCollection Date: 2024-01-01

Zhen Jiang, Ya Zhang, Liqin Wang, Hong Yang, Ling Yu

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引用次数: 0

Abstract

Purpose: This study identified the genetic causes of Axenfeld-Rieger syndrome (ARS) in a Chinese family and evaluated their clinical phenotype and clinical treatment.

Methods: We recruited a Chinese family with ARS. The proband presented with bilateral ectopic pupils, periumbilical redundancy, craniofacial abnormalities, and dental abnormalities after birth and was diagnosed with ARS. The symptoms were the same for her younger brother. Blood samples were collected from four family members: the proband, her brother, and her parents. Whole-genome sequencing (WGS) was performed to identify probable genetic variants in the proband. To confirm the identified variants, samples from the other family members were subjected to quantitative polymerase chain reaction (qPCR) and Sanger sequencing.

Results: Based on the results of WGS, we suspected a deletion region and an inversion region around the PITX2 gene. Through qPCR and Sanger sequencing, we identified a complex rearrangement involving a 6.15 Mb deletion on Chromosome 4, including the PITX2 coding region (Hg38; chr4:110617776-116769011), a 45.71 Mb inversion (Hg38; chr4:116769011-162481408), and a 14-bp deletion (Hg38; chr4:162481409-162481422). Interestingly, the father's copy number was normal, but Sanger sequencing revealed the same breakpoints. This indicated that the father is a balanced rearrangement carrier, and the children are unbalanced rearrangement carriers. While similar deletions and many breakpoints in this region have been reported, this specific rearrangement is novel.

Conclusions: Using WGS, qPCR, and Sanger, we found a complex genomic rearrangement with the deletion of PITX2 in a Chinese family with ARS. The clinical characteristics of the affected individuals were reported. The current findings broaden our understanding of the phenotype and variant spectrum associated with ARS caused by PITX2 deletion.

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目的：本研究确定了一个中国家族中阿森费尔德-里格综合征（ARS）的遗传原因，并对其临床表型和临床治疗进行了评估：方法：我们招募了一个患有阿森费尔德-里格综合征的中国家庭。方法：我们招募了一个患有阿森费尔德-里格综合征（ARS）的中国家庭。原告出生后出现双侧异位瞳孔、脐周赘生物、颅面畸形和牙齿畸形，被诊断为 ARS。她的弟弟也有同样的症状。研究人员采集了四名家庭成员的血样：原型、她的弟弟和她的父母。进行了全基因组测序 (WGS)，以确定该患者可能存在的基因变异。为了确认所发现的变异，对其他家庭成员的样本进行了定量聚合酶链反应（qPCR）和桑格测序：根据 WGS 的结果，我们怀疑 PITX2 基因周围存在一个缺失区和一个反转区。通过 qPCR 和 Sanger 测序，我们确定了一个复杂的重排，涉及 4 号染色体上 6.15 Mb 的缺失，包括 PITX2 编码区（Hg38；chr4:110617776-116769011）、45.71 Mb 的倒位（Hg38；chr4:116769011-162481408）和 14-bp 的缺失（Hg38；chr4:162481409-162481422）。有趣的是，父亲的拷贝数正常，但桑格测序却发现了相同的断点。这表明父亲是平衡重排携带者，而孩子是非平衡重排携带者。虽然该区域的类似缺失和许多断点已有报道，但这一特定的重排是新发现的：利用 WGS、qPCR 和 Sanger，我们在一个中国 ARS 家系中发现了 PITX2 缺失的复杂基因组重排。我们还报告了受影响个体的临床特征。目前的研究结果拓宽了我们对 PITX2 缺失导致的 ARS 相关表型和变异谱的理解。

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来源期刊

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.