背景:持续性肺动脉高压是一种众所周知的新生儿疾病,在大多数情况下对一氧化氮治疗和任何潜在原因的治疗反应良好。新生儿持续性肺动脉高压的遗传原因很少见。TWIST1基因参与形态遗传学,已知缺失会导致Saethre-Chotzen综合征。新生儿中从未报道过PHF14的缺失,但是动物研究表明,肺发育的严重缺陷与该基因的缺失之间存在联系。没有,据我们所知,有任何关于TWIST1和PHF14基因与新生儿持续性肺动脉高压之间联系的出版物,使这成为一个新颖的发现。
方法:我们描述了一名非近亲白人父母出生的白人男性新生儿;他表现出畸形特征和治疗难治性持续性肺动脉高压。基于阵列的比较基因组杂交显示在7号染色体上存在14.7Mb间质缺失,包括TWIST1和PHF14基因。
结论:TWIST1基因可以解释我们患者的畸形特征。他有严重的持续性肺动脉高压,然而,之前没有与TWIST1基因一起描述过,但可以通过PHF14的参与来解释,这与动物实验中的发现一致,该实验表明,致命性呼吸衰竭伴有PHF14的消耗。这些发现是新颖的,对于新生儿重度持续性肺动脉高压和畸形特征的新生儿的临床管理和诊断检查具有重要意义。
BACKGROUND: Persistent pulmonary hypertension is a well-known disease of the newborn that in most cases responds well to treatment with nitric oxide and treatment of any underlying causes. Genetic causes of persistent pulmonary hypertension of the newborn are rare. The TWIST1 gene is involved in morphogenetics, and deletions are known to cause Saethre-Chotzen syndrome. Deletions of PHF14 have never been reported in neonates, but animal studies have shown a link between severe defects in lung development and deletions of this gene. There have not, to the best of our knowledge, been any publications of a link between the genes TWIST1 and PHF14 and persistent pulmonary hypertension of the newborn, making this a novel finding.
METHODS: We describe a white male neonate born at term to non-consanguineous white parents; he presented with dysmorphic features and a therapy-refractory persistent pulmonary hypertension. Array-based comparative genomic hybridization revealed the presence of a 14.7 Mb interstitial deletion on chromosome 7, encompassing the genes TWIST1 and PHF14.
CONCLUSIONS: The TWIST1 gene can explain our patient\'s dysmorphic features. His severe persistent pulmonary hypertension has, however, not been described before in conjunction with the TWIST1 gene, but could be explained by involvement of PHF14, consistent with findings in animal experiments showing lethal respiratory failure with depletion of PHF14. These findings are novel and of importance for the clinical management and diagnostic workup of neonates with severe persistent pulmonary hypertension of the newborn and dysmorphic features.