TMEM100在新生儿腺泡发育不良和一种新的TBX4变异中表达减少:一例报告。

IF 1.3 4区 医学 Q3 PATHOLOGY
Pediatric and Developmental Pathology Pub Date : 2024-05-01 Epub Date: 2023-12-03 DOI:10.1177/10935266231213464
Przemyslaw Szafranski, Silvia Patrizi, Tomasz Gambin, Bushra Afzal, Emily Schlotterbeck, Justyna A Karolak, Gail Deutsch, Drucilla Roberts, Paweł Stankiewicz
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引用次数: 0

摘要

肺腺泡发育不良(AcDys)是一种罕见的新生儿致命性发育障碍,其特征是严重呼吸衰竭和肺动脉高压难以治疗。最近,在涉及TBX4、FGF10或FGFR2的杂合单核苷酸变异或拷贝数变异缺失导致的AcDys患者中,有报道称TBX4-FGF10-FGFR2- tmem100信号调节肺发育的异常。在这里,我们描述了一个女性新生儿谁死于4小时,由于严重的呼吸窘迫相关的死后尸检组织病理学评估诊断AcDys。基因组分析显示,TBX4中存在一种新的有害杂合错义变异C . 728a >C (p.Asn243Thr),该变异在父本第17号染色体上重新产生。我们还在TBX4编码变体的TBX4增强子中发现了6个候选的半胚罕见变异。先证者肺组织的基因表达分析显示,免疫组织化学显示TMEM100表达显著降低,动脉和毛细血管内皮中几乎没有TMEM100表达。这些结果支持了检测到的TBX4变异的致病性,并提供了进一步的证据,表明TBX4和TMEM100之间的信号传导中断可能导致人类严重的肺部表型,包括AcDys。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Diminished TMEM100 Expression in a Newborn With Acinar Dysplasia and a Novel TBX4 Variant: A Case Report.

Acinar dysplasia (AcDys) of the lung is a rare lethal developmental disorder in neonates characterized by severe respiratory failure and pulmonary arterial hypertension refractory to treatment. Recently, abnormalities of TBX4-FGF10-FGFR2-TMEM100 signaling regulating lung development have been reported in patients with AcDys due to heterozygous single-nucleotide variants or copy-number variant deletions involving TBX4, FGF10, or FGFR2. Here, we describe a female neonate who died at 4 hours of life due to severe respiratory distress related to AcDys diagnosed by postmortem histopathologic evaluation. Genomic analyses revealed a novel deleterious heterozygous missense variant c.728A>C (p.Asn243Thr) in TBX4 that arose de novo on paternal chromosome 17. We also identified 6 candidate hypomorphic rare variants in the TBX4 enhancer in trans to TBX4 coding variant. Gene expression analyses of proband's lung tissue showed a significant reduction of TMEM100 expression with near absence of TMEM100 within the endothelium of arteries and capillaries by immunohistochemistry. These results support the pathogenicity of the detected TBX4 variant and provide further evidence that disrupted signaling between TBX4 and TMEM100 may contribute to severe lung phenotypes in humans, including AcDys.

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来源期刊
CiteScore
3.70
自引率
5.30%
发文量
59
审稿时长
6-12 weeks
期刊介绍: The Journal covers the spectrum of disorders of early development (including embryology, placentology, and teratology), gestational and perinatal diseases, and all diseases of childhood. Studies may be in any field of experimental, anatomic, or clinical pathology, including molecular pathology. Case reports are published only if they provide new insights into disease mechanisms or new information.
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