LAUSR

To the Editor, Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) caused by gene variants that lead to a failure of functional T cell development, with or without accompanying defects in the production of B and/or NK cells [1]. Deleterious variants in more than 20 genes have been implicated in SCID [2]. The FOXN1 (Forkhead Box N1) deficiency, also known as the nude SCID, is a very rare autosomal recessive form of SCIDs. It has a unique phenotype with severe T cell immunodeficiency with normal B and NK cells, thymus dysgenesis, congenital alopecia, and nail dystrophy [3]. Due to the pleiotropic effects of FOXN1, the patients present with nonimmunological features in addition to the classical TBNK SCID, with mainly the skin and hair being affected including abnormal hair keratinization and absence of hair [4]. FOXN1 gene (located in 17q11.2) encodes a transcription factor that regulates the development, differentiation, and function of thymic epithelial cells (TECs) both in the prenatal and postnatal thymus [5, 6]. FOXN1 mutations disrupt T cell lineage commitment, development, and selection [7]. Currently three different variants (p.R255*, p.R320W, and p.S188fs) have been reported in the different domains of FOXN1 [8–10]. In this report, we describe the clinical features of two siblings with nude SCID phenotype who are homozygous for a novel variant in FOXN1. A two-month-old male (P1), born to consanguineous parents (second-degree cousins) presented with pneumonia, otitis, diarrhea, and absence of a thymus (Fig. S1) and was diagnosed with TBNK SCID. Although the patient was referred to a bone marrow transplantation center, the family refused any further diagnostic tests or treatment; he died at home 1 month after diagnosis. Fourteen months after the passing of their first child, the mother gave birth to a daughter (P2), who suffered from oral candidiasis, recurrent lung infections, and sepsis. Immunophenotyping results showed T cell deficiency and although she had very low amount of B and NK cells, due to a very low absolute lymphocyte count, she was diagnosed as TBNK SCID (Table S1). P2 was referred for hematopoietic stem cell transplantation (HSCT) from a HLA-match unrelated donor. An amplicon-based targeted next generation sequencing (NGS) panel that contains 18 of the most common SCIDrelated genes (IL2RG, JAK3, L7RA, PTPRC, CD3D, CD3E, CD3Z, CORO1A, DCLRE1C, PRKCD, AK2, ADA, RAG1,