Expanding the neurodevelopmental phenotype of PURA syndrome.
Expanding the neurodevelopmental phenotype of PURA syndrome.
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DOI：
10.1002/ajmg.a.38521
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Paciorkowski AR
中科院分区：
文献类型：
--
作者：
Lee BH;Reijnders MRF;Abubakare O;Tuttle E;Lape B;Minks KQ;Stodgell C;Bennetto L;Kwon J;Fong CT;Gripp KW;Marsh ED;Smith WE;Huq AM;Coury SA;Tan WH;Solis O;Mehta RI;Leventer RJ;Baralle D;Hunt D;Paciorkowski AR
Pura综合征是一种新近报道的发育性脑病，以新生儿低眼压、喂养困难、全球发育迟缓、严重智能障碍以及频繁的呼吸暂停和癫痫为特征。我们描述了18个在Pura中具有杂合序列变异的新个体。一种神经运动障碍始于新生儿的低张力，但最终导致进展延迟到行走，几乎所有人都存在这种障碍。先天性呼吸暂停在婴儿期出现的比例为56%，但该队列中的所有病例在出生后第一年都得到了解决。经常报告喂养困难，28%的患者需要放置胃造瘘管。50%的受试者出现癫痫，包括婴儿痉挛和Lennox-Gastaut综合征。骨科并发症发生率为39%。胃肠动力障碍和眼球震颤也是反复发作的特征。一名患者被诊断为自闭症，这可能扩大了与该综合征相关的神经发育表型。然而，我们没有在120名自闭症患者的队列中发现额外的Pura序列变异。我们还介绍了Pura综合征的第一次神经病理学研究，并描述了深部白质内小动脉周围的慢性炎性变化。我们没有发现突变类别和严重程度之间的显著相关性，也没有发现PUR重复结构域中序列变异的位置之间的显著相关性。需要在更大的Pura综合征受试者队列中进行进一步的研究，以澄清这些基因-表型的关联。
PURA syndrome is a recently described developmental encephalopathy presenting with neonatal hypotonia, feeding difficulties, global developmental delay, severe intellectual disability, and frequent apnea and epilepsy. We describe 18 new individuals with heterozygous sequence variations in PURA. A neuromotor disorder starting with neonatal hyptonia, but ultimately allowing delayed progression to walking, was present in nearly all individuals. Congenital apnea was present in 56% during infancy, but all cases in this cohort resolved during the first year of life. Feeding difficulties were frequently reported, with gastrostomy tube placement required in 28%. Epilepsy was present in 50% of the subjects, including infantile spasms and Lennox-Gastaut syndrome. Skeletal complications were found in 39%. Disorders of gastrointestinal motility and nystagmus were also recurrent features. Autism was diagnosed in one individual, potentially expanding the neurodevelopmental phenotype associated with this syndrome. However we did not find additional PURA sequence variations in a cohort of 120 subjects with autism. We also present the first neuropathologic studies of PURA syndrome, and describe chronic inflammatory changes around the arterioles within the deep white matter. We did not find significant correlations between mutational class and severity, nor between location of the sequence variation in PUR repeat domains. Further studies are required in larger cohorts of subjects with PURA syndrome to clarify these genotype-phenotype associations.
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