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Case Reports
. 2024 Aug 1;46(6):e472-e475.
doi: 10.1097/MPH.0000000000002862. Epub 2024 May 14.

Clinical and Immunologic Features of a Patient With Homozygous FNIP1 Variant

Selami Ulaş  1 , Sezin Naiboğlu  1 , İsa Özyilmaz  2 , Asli Güner Öztürk Demir  3 , Işilay Turan  1 , Sabahattin Yuzkan  4 , Akif Ayaz  3 , Mehmet Halil Çeliksoy  1
Affiliations
Case Reports

Clinical and Immunologic Features of a Patient With Homozygous FNIP1 Variant

Selami Ulaş et al. J Pediatr Hematol Oncol. .

Abstract

Agammaglobulinemia represents the most profound primary antibody deficiency, stemming from early cessation of B-cell development. Deficiency in folliculin-interacting protein 1 (FNIP1) is a novel inborn error of immunity characterized by a severe defect in B-cell development, agammaglobulinemia, variable neutropenia, and hypertrophic cardiomyopathy. FNIP1 plays a critical role in B-cell development and metabolic homeostasis, establishing a metabolic checkpoint that ensures pre-B cells possess sufficient metabolic capacity to undergo division while concurrently limiting lymphogenesis due to abnormal growth. Disruption of FNIP1 functionality affects the fundamental metabolic regulators adenosine monophosphate-activated protein kinase and mTOR, culminating in a severe B-cell deficiency alongside hypogammaglobulinemia, hypertrophic cardiomyopathy, preexcitation syndrome, and intermittent neutropenia. This case report presents an 11-month-old male patient with FNIP1 deficiency who, in addition to classical features, exhibited posterior cerebellar hypoplasia.

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Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Niehues T, Ozgur TT, Bickes M, et al. Mutations of the gene FNIP1 associated with a syndromic autosomal recessive immunodeficiency with cardiomyopathy and preexcitation syndrome. Eur J Immunol. 2020;50:1078–1080.
    1. Saettini F, Poli C, Vengoechea J, et al. Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency. Blood. 2021;137:493–499.
    1. Ben-Ali M, Kechout N, Mekki N, et al. Genetic approaches for definitive diagnosis of agammaglobulinemia in consanguineous families. J Clin Immunol. 2020;40:96–104.
    1. Park H, Staehling K, Tsang M, et al. Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte development. Immunity. 2012;36:769–781.
    1. Baba M, Hong SB, Sharma N, et al. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci USA. 2006;103:15552–15557.

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