Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency

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dc.contributor.authorSaettini, Francesco
dc.contributor.authorPoli, Cecilia
dc.contributor.authorVengoechea, Jaime
dc.contributor.authorBonanomi, Sonia
dc.contributor.authorOrellana, Julio C.
dc.contributor.authorFazio, Grazia
dc.contributor.authorRodriguez, Fred H.
dc.contributor.authorNoguera, Loreani
dc.contributor.authorBooth, Claire
dc.contributor.authorJarur-Chamy, Valentina
dc.contributor.authorShams, Marissa
dc.contributor.authorIascone, María
dc.contributor.authorVukic, Maja
dc.contributor.authorGasperini, Serena
dc.contributor.authorQuadri, Manuel
dc.contributor.authorBarroeta Seijas, Amairelys
dc.contributor.authorRivers, Elizabeth
dc.contributor.authorMauri, Mario
dc.contributor.authorBadolato, Raffaele
dc.contributor.authorCazzaniga, Gianni
dc.contributor.authorBugarin, Cristina
dc.contributor.authorGaipa, Giuseppe
dc.contributor.authorKroes, Wilma G. M.
dc.contributor.authorMoratto, Daniele
dc.contributor.authorOostaijen-Ten Dam, Monique M. van
dc.contributor.authorBaas, Frank
dc.contributor.authorMaarel, Silvère van der
dc.contributor.authorPiazza, Rocco
dc.contributor.authorCoban-Akdemir, Zeynep H.
dc.contributor.authorLupski, James R.
dc.contributor.authorYuan, Boi
dc.contributor.authorDaxinger, Lucia
dc.contributor.authorBiondi, Andrea
dc.contributor.authorChinn, Ivan K.
dc.date.accessioned2021-08-23T15:30:18Z
dc.date.available2021-08-23T15:30:18Z
dc.date.issued2020
dc.description.abstractAgammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated three novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound heterozygous variants in the gene for Folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and PI3K/AKT pathway, was impaired. These defects recapitulated the Fnip1 -/- animal model. Moreover, we identified either uniparental disomy or copy number variants [CNV] in two patients, expanding the variant spectrum of this novel inborn error of immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity.es
dc.identifier.citationBlood, 2021 Jan, vol.137(4):493-499es
dc.identifier.urihttps://dx.doi.org/10.1182/blood.2020006441es
dc.identifier.urihttp://hdl.handle.net/11447/4422
dc.language.isoenes
dc.subjectAgammaglobulinemiaes
dc.subjectImmunologic Deficiency Syndromeses
dc.subjectGeneticses
dc.titleAbsent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiencyes
dc.typeArticlees

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