Martin Liska, Czech Republic
University Hospital Pilsen Department of Immunology and AllergologyPresenter of 1 Presentation
NFKB2 MUTATION DIAGNOSED BY WHOLE EXOME SEQUENCING (WES) IN A PATIENT WITH COMPLEX PHENOTYPE AND HYPOGAMMAGLOBULINEMIA
Abstract
Background and Aims
The onset of next-generation sequencing (NGS), especially sequencing of the whole genome (WGS) or exome (WES), allows the identification of rare gene mutations underlying inherited disorders of the immune system.
Methods
At the department of immunology in Pilsen,1 a boy aged four years with recurrent infections was diagnosed to have severe hypogammaglobulinemia and disturbed specific antibody response. Since his B cell count was normal, the diagnosis of early onset common variable immunodeficiency (CVID) was established, and immunoglobulin substitution was stared. Six months later, he required hydrocortisone substitution for central hypocorticism and congenital malformations of the central nervous system (hydrosyringomyelia, Chiari malformation) were revealed; the latter was resolved by surgical intervention. Within several years, the patient’s B cell count decreased progressively, and he required an increased dosage of immunoglobulin substitution. Later, he developed several autoimmune features, such as thyroiditis, vitiligo and total alopecia along with nail dystrophy and osteoporosis, which resulted in fractures of thoracic vertebrae.
Results
The described complex symptomatology encouraged us to perform WES in Prague research center2,3 that identified a heterozygous mutation c.2557C˃T (NM_001261403.2, p.Arg853*) in NFKB2 gene which was previously described in a single patient with similar symptomatology. WES finding was confirmed by Sanger sequencing.
Conclusions
NGS is a robust modern genetic method allowing us to establish an accurate diagnosis in patients with suspected primary immunodeficiency, but atypical or rare symptomatology. Such precise diagnostics allows individually tailored management of the diseases.