De novo missense variants in the RAP1B gene identified in two patients with syndromic thrombocytopenia.,Clinical Genetics

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De novo missense variants in the RAP1B gene identified in two patients with syndromic thrombocytopenia.
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-07-06 , DOI: 10.1111/cge.13807
Jan Hendrik Niemann ₁ , Chen Du ₁ , Susanne Morlot ₁ , Gunnar Schmidt ₁ , Bernd Auber ₁ , Beate Kaune ₁ , Gudrun Göhring ₁ , Tim Ripperger ₁ , Brigitte Schlegelberger ₁ , Winfried Hofmann ₁ , Thomas Smol ₂ , Emilie Ait-Yahya ₃ , Anna Raimbault ₄ , Anne Lambilliotte ₅ , Florence Petit ₆ , Doris Steinemann ₁

Affiliation

We present two independent cases of syndromic thrombocytopenia with multiple malformations, microcephaly, learning difficulties, dysmorphism and other features. Exome sequencing identified two novel de novo heterozygous variants in these patients, c.35G>T p.(Gly12Val) and c.178G>C p.(Gly60Arg), in the RAP1B gene (NM_001010942.2). These variants have not been described previously as germline variants, however functional studies in literature strongly suggest a clinical implication of these two activating hot spot positions. We hypothesize that pathogenic missense variants in the RAP1B gene cause congenital syndromic thrombocytopenia with a spectrum of associated malformations and dysmorphism, possibly through a gain of function mechanism.

中文翻译：

在两名患有血小板减少症的患者中发现了RAP1B基因的从头错义变异。

我们介绍了两个独立的综合征性血小板减少症，具有多种畸形，小头畸形，学习困难，畸形和其他特征。外显子组测序在RAP1B基因（NM_001010942.2）中确定了这些患者中的两个新的从头杂合变异，即c.35G> T p。（Gly12Val）和c.178G> C p。（Gly60Arg）。这些变体以前没有被描述为种系变体，但是文献中的功能研究强烈暗示了这两个激活热点位置的临床意义。我们假设RAP1B中的致病性错义变异基因可能导致先天性综合征性血小板减少症，并伴有一系列相关的畸形和畸形，可能是通过功能机制获得的。

更新日期：2020-07-06

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