Further delineation of putative ACTB loss‐of‐function variants: A 4‐patient series,Human Mutation

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Further delineation of putative ACTB loss‐of‐function variants: A 4‐patient series
Human Mutation ( IF 3.3 ) Pub Date : 2020-01-16 , DOI: 10.1002/humu.23970
Matthias Baumann ₁ , Erin M Beaver ₂ , María Palomares-Bralo ₃ , Fernando Santos-Simarro ₃ , Peter Holzer ₄ , Gundula Povysil ₅ , Thomas Müller ₁ , Taras Valovka ₁ , Andreas R Janecke _{1,

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Affiliation

ACTB encodes β‐cytoplasmic actin, an essential component of the cytoskeleton. Based on chromosome 7p22.1 deletions that include the ACTB locus and on rare truncating ACTB variants, a phenotype resulting from ACTB haploinsufficiency was recently proposed. We report putative ACTB loss‐of‐function variants in four patients. To the best of our knowledge, we report the first 7p22.1 microdeletion confined to ACTB and the second ACTB frameshifting mutation that predicts mRNA decay. A de‐novo ACTB p.(Gly302Ala) mutation affects β‐cytoplasmic actin distribution. All four patients share a facial gestalt that is distinct from that of individuals with dominant‐negative ACTB variants in Baraitser‐Winter cerebrofrontofacial syndrome. Two of our patients had strikingly thin and sparse scalp hair. One patient had sagittal craniosynostosis and hypospadias. All three affected male children have attention deficits and mild global developmental delay. Mild intellectual disability was present in only one patient. Heterozygous ACTB deletion can allow for normal psychomotor function.

中文翻译：

进一步描述推定的ACTB功能丧失的变体：4位患者的系列

ACTB编码β细胞质肌动蛋白，它是细胞骨架的重要组成部分。基于包括ACTB基因座的染色体7p22.1缺失和罕见的截短ACTB变体，最近提出了由ACTB单倍体不足引起的表型。我们报告了四名患者的假定的ACTB功能丧失变异。据我们所知，我们报道了第一个7p22.1微缺失仅限于ACTB 和第二个ACTB移码突变，该突变预测了mRNA的降解。创新的ACTBp。（Gly302Ala）突变会影响β细胞质肌动蛋白的分布。这四例患者的面部姿势完全不同于Baraitser-Winter脑额面部综合征中ACTB显性阴性的个体。我们的两名患者头皮稀疏稀疏。1例患者有矢状颅突和尿道下裂。所有三个受影响的男孩都有注意力缺陷和轻度的全球发育迟缓。仅一名患者存在轻度智力障碍。杂合ACTB缺失可以使精神运动功能正常。

更新日期：2020-03-26

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