Expanding the phenotypic spectrum associated with DPF2: A new case report
Expanding the phenotypic spectrum associated with DPF2: A new case report
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DOI：
10.1002/ajmg.a.61262
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发表时间：
2019-08-01
影响因子：
2
通讯作者：
Bicknell, Louise S.
中科院分区：
文献类型：
--
作者：
Knapp, Karen M.;Poke, Gemma;Bicknell, Louise S.
Coffin-Siris综合征（CSS）是一种临床和遗传异质性发育障碍，与BAF染色质重塑复合体的破坏有关。最近，在具有CSS的一些共同特征的患者中，DPF2出现了新生错义和截断变异体。在这里，我们报告了另一个携带新的错义DPF2变异的个体，c.1066T >g, p.Cys356Gly。结构模型表明，预测的氨基酸取代影响锌离子配位所需的核心残基，并可能改变DPF2的PHD2结构域结构。Pierre Robin序列和膈疝的临床表现不能立即提示CSS，更常见的CSS特征是趾甲发育不全和特征面部特征非常微妙。这个个体进一步拓宽了dpf2相关CSS的表型特征，以及更普遍的CSS。
Coffin-Siris syndrome (CSS) is a clinically and genetically heterogeneous developmental disorder, linked to disruption of the BAF chromatin-remodeling complex. Recently, de novo missense and truncating variants have been reported in DPF2 in patients sharing some of the common features of CSS. Here we report a further individual harboring a novel de novo missense DPF2 variant, c.1066T>G, p.Cys356Gly. Structural modeling indicated that the predicted amino acid substitution affects a core residue required for zinc ion coordination and would likely alter the PHD2 domain structure of DPF2. The clinical presentation of Pierre Robin sequence and diaphragmatic hernia did not immediately suggest CSS, with the more common CSS features of hypoplastic toenails and characteristic facial features very subtle. This individual further broadens the phenotypic features of DPF2-related CSS, as well as CSS more generally.