Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Clinical genetics, 2020-10, Vol.98 (4), p.374-378

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. 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