Background: The Forkhead box protein N1 (FOXN1) is a key regulator of thymic epithelial development, and its complete deficiency leads to a nude-severe combined immunodeficiency (SCID) phenotype. More recently, heterozygous mutations in FOXN1 have been linked with a syndrome of congenital lymphopenia and a wide clinical spectrum, with most cases being caused by missense mutations.Aim: To broaden the genotypic and phenotypic spectrum of heterozygous FOXN1 deficiency.Methods: Case report of a patient with FOXN1 haploinsufficiency due to a novel splice-site mutation.Results: Our patient was identified at 3 weeks of life given an abnormal newborn screen (NBS) for SCID, and was found to have congenital lymphopenia preferentially affecting CD8⁺ T-cells. Her cellular and humoral function were both excellent, and she has remained entirely asymptomatic and thriving for the first 3 years of her life. The patient was found on whole exome sequencing to carry a heterozygous splice-site mutation in the FOXN1 gene, affecting the Forkhead domain. The mutation was also identified in her asymptomatic mother.Conclusion: Heterozygous FOXN1 mutations are an increasingly-recognized cause of congenital lymphopenia. Our experience suggests most patients remain clinically well, with main manifestation including T-lymphopenia, mostly affecting CD8⁺ cells. Identification of the same variant in an asymptomatic parent suggests age-dependent improvement in T-cell counts and an overall benign course, while provides impetus for diligent conservative management with regular follow-up.Statement of novelty: Heterozygous FOXN1 deficiency is a relatively new entity, attributed in most cases to missense mutations in FOXN1. To further expand the knowledge basis regarding this emerging disorder, as well as its genotypic repertoire, we herein report a case of heterozygous FOXN1 deficiency caused by a splice site mutation.

Introduction: The nuclear factor-kB (NF-kB) signaling pathway plays a major role in mediating multiple cellular processes, including immune and inflammatory responses.Aims: We describe the histopathological findings of lymph nodes from a patient with a homozygous NF-kB subunit 1 (NF-kB1) mutation causing a combined immunodeficiency phenotype.Results: A nodal biopsy was performed for lymphadenopathy evaluation, in the context of development of persistent EBV infection. Our findings show that this patient has normal lymph node tissue present, however, abnormal histopathology features were observed, including atrophic germinal centers. B cell subset components within the B cell domain were also analyzed. The development of the B cell response during EBV infection was found to be significantly impaired.Conclusion: Aberrant signaling due to NF-kB1 deficiency has a significant impact on the development of B cell immunoproliferative responses.Statement of novelty: We report on the abnormal histopathology findings of lymph node biopsy from a patient with homozygous NF-kB1 mutation.

A diagnosis of immunodeficiency can be challenging for families as they navigate the emotional impact of this diagnosis, as well as the potential financial burden of treatment. For rare diseases such as primary immunodeficiency (PI), patients are often required to take a proactive role in managing their own care and may be engaged with health care providers who have minimal experience with PI disease. These providers may also have limited access to information on the resources available for this population. A review of the information available showed that a paucity of information existed for these families who were looking for appropriate resources related to their diagnosis. The PI Social Work Network was established in 2011 by Immunodeficiency Canada to develop a network of social workers across Canada who work with patients diagnosed with PI. This network has had a focus on support programs, education, and research. Resource guides were created by the network to support families by providing information on both provincial as well as national resources available. While these lists are not exhaustive, there is an attempt to keep them as up to date as possible. If additional psychosocial support would be beneficial or a family requires support accessing resources, they should be directed to their local hospital social worker, or they may contact Wendy Shama, MSW, RSW, at Immunodeficiency Canada.Statement of novelty: National and provincial resources guides have been created for families and individuals affected by primary immunodeficiency.