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A case study of primary immunodeficiency in a personalized medicine diagnostic perspective: novel mutations in an ataxia telangiectasia patient identified by next generation sequencing (CROSBI ID 650732)

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Zenić, Lucija ; Polančec, Denis ; Živković, Jelena ; Bulat Lokas, Sandra ; Vlahoviček, Kristian ; Turkalj, Mirjana A case study of primary immunodeficiency in a personalized medicine diagnostic perspective: novel mutations in an ataxia telangiectasia patient identified by next generation sequencing // ISABS conference : abstracts. 2017. str. xx-xx

Podaci o odgovornosti

Zenić, Lucija ; Polančec, Denis ; Živković, Jelena ; Bulat Lokas, Sandra ; Vlahoviček, Kristian ; Turkalj, Mirjana

engleski

A case study of primary immunodeficiency in a personalized medicine diagnostic perspective: novel mutations in an ataxia telangiectasia patient identified by next generation sequencing

In a translational medicine concept, we aim to combine clinical, immunological and genetic aspects of the primary immunodeficiency diagnostics in order to improve treatment decisions and prevention strategies of these disorders. In this approach, the assessment of the immune imbalance by flow cytometry combined with the next generation sequencing (NGS) technology represents an unprecedented tool in immunogenetic diagnostics of rare and monogenic diseases in the new era of precision medicine. A 16 year-old male patient has been admitted to our hospital due to recurrent respiratory infections and hypogammaglobulinemia, and was diagnosed with ataxia telangiectasia (A-T)-a rare genetic disorder of neurologic impairment and immune deficiency. We performed the flow cytometry immunophenotyping of peripheral blood using a 6- and 7-colour antibody panels for the analysis of T cells, B cells and NK cells (Table 1, Panel 1 and 2) and the B cell subsets (Table 2), as well as the targeted NGS analysis using the TrueSeq Custom Amplicon panel and the TruSeq Custom Amplicon Low Imput kit followed by sequencing on the MiniSeq system (Illumina, USA) to screen for the variants of the immunodeficiency genes involved in the predominantly antibody deficiency and combined immunodeficiencies with associated or syndromic features (Table 3, Panel 1 and 2). Immunophenotyping revealed a decrease or a complete loss of the CD4+ T lymphocytes, B lymphocytes, transitional B lymphocytes, class- switched memory B lymphocytes and plasmablasts (the latter not shown) ; an increase of the CD3+HLA-DR+ activated T lymphocytes (Figure 1) ; and an appearance of a peculiar CD45dimCD38++CD27+CD56+ population (Figure 2). The targeted NGS analysis identified 3 novel missense variants in i) meiotic recombination 11 (MRE11) gene, ii) ataxia telangiectasia and Rad3-related protein (ATR) gene, and iii) B-cell linker protein (BLNK) gene, with the in silico predictions as possibly deleterious (Figure 3). We here report novel variants detected by NGS in the A-T patient previously not reported in clinical practice. Given their potentially pathogenic nature, i.e. the phenotypic association with leukemia (BLNK gene), the appearance of the CD45dimCD38+CD27+CD56+ population, and an increased alpha-fetoprotein level, a further treatment of the patient requires a close monitoring for the potential development of malignancy - the main cause of premature death of A-T patients, by means of a tight integration of immunogenetic diagnostic tools in a personalized medicine perspective.

Respiratory infection, flow cytometry, sequencing (NGS) technology

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Podaci o prilogu

xx-xx.

2017.

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objavljeno

Podaci o matičnoj publikaciji

ISABS conference : abstracts

Podaci o skupu

ISABS conference

poster

19.06.2017-24.06.2017

Dubrovnik, Hrvatska

Povezanost rada

Kliničke medicinske znanosti