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

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.
PMID: 32627184 [PubMed - as supplied by publisher]

Source: Clinical Genetics - July 5, 2020 Category: Genetics & Stem Cells Authors: Niemann JH, Du C, Morlot S, Schmidt G, Auber B, Kaune B, Göhring G, Ripperger T, Schlegelberger B, Hofmann W, Smol T, Ait-Yahya E, Raimbault A, Lambilliotte A, Petit F, Steinemann D Tags: Clin Genet Source Type: research