AUTHOR=Kwon Won Kyung , Kim Jee Ah , Park Jong-Ho , Kim Doo Ri , Park Su Eun , Kim Yae Jean , Yoo Keon Hee , Jang Ja-Hyun , Kang Eun Suk 

TITLE=Case Report: Novel Splicing Variant in SH2D1A in a Patient With X-Linked Lymphoproliferative Syndrome Type 1

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.812590

DOI=10.3389/fped.2022.812590

ISSN=2296-2360

ABSTRACT=<p>X-linked lymphoproliferative disease type 1 (XLP1), an X-linked recessive genetic disorder, is associated with primary immunodeficiency. Patients with XLP1 are susceptible to Epstein–Barr virus (EBV) infection. <italic>SH2D1A</italic> gene is known as the causative gene. We found a novel hemizygous variant of <italic>SH2D1A</italic>, c.162_201+31delinsTACAAGGACATATACA, from a 5-year-old male patient who had been diagnosed with EBV infection and Hodgkin's lymphoma. In targeted next-generation sequencing (NGS), complex variants at exon 2 were not consistently identified with two software programs. They showed a soft-clipped read pattern. The variant had a 71-bp deletion and a 16-bp insertion across exon 2 as confirmed by direct sequencing. As the variant was located within the exon–intron boundary, two aberrant transcripts were shown by RNA study. Although NGS method has a limitation in detecting large deletion/duplication variants, proper bioinformatics pipeline and careful review of data might enable the detection of complex variants.</p>