Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome
Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome
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进一步描述截短 KMT2A 突变的表型：扩展的 Wiedemann-Steiner 综合征。
DOI：
10.1002/ajmg.a.38025
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发表时间：
2017-02-01
影响因子：
2
通讯作者：
Yu, Yongguo
中科院分区：
文献类型：
--
作者：
Sun, Yu;Hu, Guorui;Yu, Yongguo
KMT2A突变导致Wiedemann-Steiner综合征（WDSTS），其特征是多毛，身材矮小，面部特征明显。在这里，我们报告了两名中国男孩具有新的无义KMT2A突变。大部分表型与WDSTS一致。然而，他们缺乏WDSTS的关键特征——肘多毛症。此外，他们的横向掌纹不存在。我们进一步总结了KMT2A突变携带者的基因型和表型。普遍的表型包括出生后生长迟缓、发育迟缓、身材矮小和智力残疾。常见的面部特征有：浓眉、长睫毛、下斜、睑裂窄、鼻梁宽、鼻尖宽。他们有全身性多毛症。在KMT2A突变患者中，可以观察到多毛的背部和多毛的肘部。手掌近端横纹缺失仅见于这两名中国男孩。这可能是由于种族背景的差异。到目前为止，KMT2A的所有突变都位于FYRC结构域之前。它们会截断KMT2A mRNA转录本。因此，组蛋白甲基转移酶活性的单倍不足会影响转录调节。(c) 2016 Wiley Periodicals, Inc.；
KMT2A mutations cause Wiedemann-Steiner syndrome (WDSTS), which is characterized by hypertrichosis cubiti, short stature, and distinct facial features in general. Here, we report two Chinese boys with novel nonsense KMT2A mutations. Most of their phenotypes are concordant with WDSTS. They, however, lack the key WDSTS featurehypertrichosis cubiti. Additionally, their transverse palmar creases are absent. We further summarized the genotypes and phenotypes of the KMT2A mutation carriers. The consensus phenotypes include postnatal growth retardation, developmental delay, short stature, and intellectual disability. The common facial features include thick eyebrows, long eyelashes, downslanting, and narrow palpebral fissures, wide nasal bridge, and broad nasal tip. They have generalized hypertrichosis. A hairy back can be observed as frequently as hairy elbows in patients with KMT2A mutations. Absent palmar proximal transverse creases are only observed in these two Chinese boys. This might be due to the difference in ethnic background. Thus far, all mutations in KMT2A are located before the FYRC domain. They would truncate KMT2A mRNA transcripts. Haploinsufficiency of the histone methyltransferase activity would therefore influence transcriptional regulation. (c) 2016 Wiley Periodicals, Inc.