Follicular Lymphoma in a X‐linked Lymphoproliferative Syndrome Carrier Female

Abstract

X‐linked lymphoproliferative (XLP) syndrome is a rare primary immune‐deficiency disorder caused by mutations of the SH2D1A or XIAP genes. Males with the disorder are usually in good health until contracting Epstein–Barr virus (EBV) whereupon the majority of patients die from fulminant infectious mononucleosis, lymphoma or hypogammaglobulinaemia. This report describes a female carrier with an XLP phenotype who was retrospectively identified after her grandson died from the disorder. Subsequent genetic testing identified the patient's mother and affected maternal grandmother as XLP carriers. The family’s medical records were significant. The proband had lymphoma at ages 2 and 8 and made a full recovery following treatment. Both the maternal grandmother and uncle died of non‐Hodgkin’s lymphoma. We were concerned that the XLP carrier mother may be predisposed to lymphoma if the normal X chromosome is skewed towards inactivation. The human androgen receptor assay detected random X chromosome inactivation in the carrier mother. EBV was not detected in the lymphoma tissues of the proband and his grandmother, confirming previous findings that EBV is not always associated with lymphoma in XLP. More significantly, our study highlights the importance of identifying XLP in families with a high incidence of lymphoma.

Targeted sequencing identifies a novel SH2D1A pathogenic variant in a Chinese family: Carrier screening and prenatal genetic testing

“…Apart from the risk for recurrence of XLP1 mentioned above, lymphoma was also been reported in SH2D1A female carrier due to nonrandom X-inactivation [ 33 ], suggesting that carrier females in an XLP kindred might be at the risk of developing XLP phenotype and should be monitored for early symptoms. Thus, screening SH2D1A may provide early molecular diagnosis for both XLP1 patients and the potential XLP1 carriers.…”

Genetic Features of Late Onset Primary Hemophagocytic Lymphohistiocytosis in Adolescence or Adulthood

“…Viral infection, particularly EBV infection, is an important predisposing factor in HLH. Studies have shown that individuals with immune deficiencies such as X-linked lymphoproliferative syndrome (XLP) are usually asymptomatic before EBV infection, and there is no clear genotype/phenotype correlation [28]. The onset and severity of HLH disease may differ among individuals due to varying exposure to triggering factors.…”

Targeting IAPs as An Approach to Anti-Cancer Therapy

“…Both XIAP and cIAP have recently been implicated as having important roles in innate immunity to bacterial infections [105][106][107]. In addition, genetic lack of XIAP has been linked to X-linked lymphoproliferative syndrome (XLP), a condition characterized by an abnormal immune response to infection with the Epstein-Barr virus (EBV) [108,109].…”