De novo missense variants in the RAP1B gene identified in two patients with syndromic thrombocytopenia. Issue 4 (21st July 2020)

• Record Type: Journal Article
• Authors: Niemann, Jan Hendrik; Du, Chen; Morlot, Susanne; Schmidt, Gunnar; Auber, Bernd; Kaune, Beate; Göhring, Gudrun; Ripperger, Tim; Schlegelberger, Brigitte; Hofmann, Winfried; Smol, Thomas; Ait‐Yahya, Emilie; Raimbault, Anna; Lambilliotte, Anne; Petit, Florence; Steinemann, Doris
• Is Part Of: Clinical genetics. Volume 98:Issue 4(2020)
• Page Start: 374
• Page End: 378
• Publication Date: 2020-07-21
• Subjects: Kabuki syndrome -- learning difficulties -- malformations -- microcephaly -- pancytopenia -- RAP1B -- thrombocytopenia; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13807
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: 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. Abstract : Clinical phenotype: Syndromic thrombocytopenia in two patients from independent families Both variants in the RAP1B gene: Not associated with disease phenotype so far Suggested gain of function Highly conserved among species and the RAS protein family