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PubMed · 42071175

The Homozygous p.(Arg215Ter) Variant in XRCC2 Is Associated With Atypical Fanconi Anemia Without Major Hematological Abnormalities in Childhood.

Sabina Cenciarelli·Giulia Bruna Marchetti·Maria Iascone·Maria Grazia Patricelli·Sara Giangiobbe·Gabriella Cinzia Pozzobon·Miriam Nella Savini·Fabio Giglio·Alessandro Aiuti·Paola Carrera·Francesca Ferrua·Angela Peron
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Abstract

Fanconi Anemia (FA) is the most frequent inherited bone marrow failure syndrome. A role for the XRCC2 gene in FA was suspected in 2012 and confirmed in 2016, but only two affected individuals have been described thus far, and no long-term follow-up is available. Here we present two young related adults born to consanguineous parents, in whom we identified the homozygous p.(Arg215Ter) variant in XRCC2. Both patients presented with mild intellectual disability, microcephaly, distinctive facial features, short stature, thumb abnormalities, and abnormal skin pigmentation. Unlike in FA, DEB test resulted negative in peripheral blood during childhood and no cytopenia, clonal evolution, or other hematological complications were detected until the age of 19 and 20 years, respectively. Our report suggests that the homozygous p.(Arg215Ter) variant in XRRC2 causes a distinctive FA-like disorder, characterized by the typical physical characteristics seen in FA, but a lack of major hematological manifestations in childhood, and the presence of a more pronounced neurodevelopmental phenotype than that seen in FA.

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HumansFanconi AnemiaHomozygoteDNA-Binding ProteinsMaleFemalePhenotypeMutationMicrocephalyYoung AdultIntellectual DisabilityPedigreeAdultChildGenetic Predisposition to DiseaseFanconi anemiaXRCC2genomic instabilityintellectual disabilitymicrocephalyCase ReportsJournal Article

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Sabina Cenciarelli, Giulia Bruna Marchetti, Maria Iascone, Maria Grazia Patricelli, Sara Giangiobbe, Gabriella Cinzia Pozzobon, Miriam Nella Savini, Fabio Giglio, Alessandro Aiuti, Paola Carrera, Francesca Ferrua, Angela Peron. 2026-05-03. The Homozygous p.(Arg215Ter) Variant in XRCC2 Is Associated With Atypical Fanconi Anemia Without Major Hematological Abnormalities in Childhood.. https://doi.org/10.1002/ajmg.a.70171

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