Abstract
Objectives: Mutations in the neuroblastoma-amplified sequence (NBAS) gene were originally described in patients with skeletal dysplasia or isolated liver disease of variable severity. Subsequent publications reported a more complex phenotype. Among multisystemic clinical symptoms, we were particularly interested in the immunological consequences of the NBAS deficiency.Methods: Clinical and laboratory data of 3 patients ages 13, 6, and 5 in whom bi-allelic NBAS mutations had been detected via next-generation sequencing were characterized. Literature review of 23 publications describing 74 patients was performed.Results: We report three Russian patients with compound heterozygous mutations of the NBAS gene who had combined immunodeficiency characterized by hypogammaglobulinemia, low T-cells, and near-absent B-cells, along with liver disease, skeletal dysplasia, optic-nerve atrophy, and dysmorphic features. Analysis of the data of 74 previously reported patients who carried various NBAS mutations demonstrated that although the most severe form of liver disease seems to require disruption of the N-terminal or middle part of NBAS, mutations of variable localizations in the gene have been associated with some form of liver disease, as well as immunological disorders.Conclusions: NBAS deficiency has a broad phenotype, and referral to an immunologist should be made in order to screen for immunodeficiency.
Highlights
Primary immunodeficiencies (PIDs) form a heterogeneous group of inherited disorders [1] that were previously considered to be very rare diseases
We report three Russian patients with compound heterozygous mutations of the neuroblastoma-amplified sequence (NBAS) gene who had combined immunodeficiency characterized by hypogammaglobulinemia, low T-cells, and near-absent B-cells, along with liver disease, skeletal dysplasia, optic-nerve atrophy, and dysmorphic features
Analysis of the data of 74 previously reported patients who carried various NBAS mutations demonstrated that the most severe form of liver disease seems to require disruption of the N-terminal or middle part of NBAS, mutations of variable localizations in the gene have been associated with some form of liver disease, as well as immunological disorders
Summary
Primary immunodeficiencies (PIDs) form a heterogeneous group of inherited disorders [1] that were previously considered to be very rare diseases. PIDs are predominantly caused by mutations of the genes responsible for immune system development and various functions [1]. Skeletal dysplasias have been predominantly reported in association with humoral or combined immunodeficiencies [3], for instance with a large group of syndromic combined immunodeficiencies including cartilage-hair hypoplasia, Schimke immuno-osseous dysplasia, Roifman syndrome and the recently described skeletal dysplasia with neurological impairment, caused by mutations in the exostosin-like glycosyltransferase 3 (EXTL3) gene [1, 4,5,6]. Despite the multifaceted immune manifestations of this group of disorders, skeletal defects, such as facial dysmorphism, metaphyseal, or spondyloepiphyseal dysplasia with severe disproportionate short stature, short limbs and growth delay are usually the first symptoms that lead to specialists’ referral
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
