Long-term follow-up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA
Long-term follow-up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA
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DOI：
10.1186/s13039-015-0193-9
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发表时间：
2015-11-14
影响因子：
1.3
通讯作者：
Zucca, Claudio
中科院分区：
文献类型：
--
作者：
Bonaglia, Maria Clara;Zanotta, Nicoletta;Zucca, Claudio
背景：富含嘌呤元素结合蛋白 A（PURA，MIM 600473）被认为是新兴 5q31.3 微缺失综合征的关键表观基因。迄今为止，据报道，至少有 7 名受影响的个体具有重叠的 5q31.2q31.3 缺失，大小从 2.6 到 5 Mb 不等，具有共同的神经系统特征，如严重发育迟缓、新生儿肌张力低下、早期喂养困难、呼吸窘迫和脑电图异常。最近发现，从头 PURA 点突变确实足以引起严重的神经系统症状，在 5q31.2q31.3 缺失的患者中也观察到，进一步强化了该基因在 5q31.3 微缺失综合征中的致病作用。病例介绍：目前的患者，26 岁，是报道的最年长的个体，携带包含 PURA 的最小从头 5q31.2q31.3 微缺失（360 KB）。她的临床病史总结了 5q31.3 微缺失综合征儿童的主要神经发育表型。此外，该患者从青春期开始、青春期延迟和原发性闭经开始，表现出临床症状显着恶化。虽然癫痫发作在她一生中得到了成功治疗，但喂养问题显示出不良结果，她的呼吸问题增加并最终变得严重到足以导致她死亡。结论：本文报告的临床和分子研究结果提供了进一步的证据，表明 5q31.3 微缺失综合征是一种临床上可辨别的 PURA 相关疾病，并描述了一名 26 岁患者先前未报告的疾病自然演变。
Background: Purine-rich element binding protein A (PURA, MIM 600473), is considered the crucial phenocritical gene for an emerging 5q31.3 microdeletion syndrome. To date, at least seven affected individuals with overlapping 5q31.2q31.3 deletions, varying in size from 2.6 to 5 Mb, have been reported sharing neurologic features such as severe developmental delay, neonatal hypotonia, early feeding difficulties, respiratory distress and EEG abnormalities. The recent finding that de novo PURA point mutations are indeed sufficient to cause the severe neurological symptoms also observed in patients with 5q31.2q31.3 deletion further reinforces the gene's causative role in 5q31.3 microdeletion syndrome.Case presentation: The present patient, aged 26 years, is the oldest reported individual and carries the smallest de novo 5q31.2q31.3 microdeletion encompassing PURA (360 kb). Her clinical history summarizes the mainly neurodevelopmental phenotype described in children with 5q31.3 microdeletion syndrome. In addition, our patient exhibited a remarkable deterioration of clinical symptoms, starting at the beginning of adolescence, pubertal delay and primary amenorrhea. While epileptic seizures were successfully treated during her life, feeding problems showed a poor outcome, her respiratory problems increased and eventually became severe enough to cause her death.Conclusion: The clinical and molecular findings reported here provide further evidence that 5q31.3 microdeletion syndrome is a clinically discernible PURA-related disorder and describe the previously unreported natural evolution of the disease in a 26 years old patient.