First case of very late-onset FHL2 in Spain with two variants in the PRF1 gene

Ann Clin Biochem. 2023 Jun 26:45632231186076. doi: 10.1177/00045632231186076. Online ahead of print.ABSTRACTHemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disorder characterized by the proliferation and infiltration of macrophages and hyperactivated T lymphocytes that escape from the physiological control pathways and favour the existence of an environment of excessive inflammation and tissue destruction. HLH has been classified into two types: a primary or familial autosomal recessive form, caused by mutations in genes encoding proteins involved in the granule-dependent cytotoxic pathway (familial hemophagocytic lymphohistiocytosis [FHL] types 1-5); and other secondary or acquired form, generally associated with infections, malignancy, autoimmune diseases, metabolic disorders or primary immunodeficiencies. Since the first familial hemophagocytic lymphohistiocytosis-2 (FHL2) causative mutation in the PRF1 gene was described in 1999, more than 200 mutations have been identified to date. Here, we report the first case of very late-onset FHL2 in a Spanish 72-year-old female with splenomegaly, hypertriglyceridemia, hypofibrinogenemia, pancytopenia and marrow hemophagocytosis harbouring in heterozygosity two PRF1 variants proposed as causative in this study. The heterozygous mutation c.445G>A (p.Gly149Ser) identified in the exon 2 results in a missense mutation previously described as a probable pathogenic variant associated with the development of FHL2. Affecting...

Source: Clinical Biochemistry - June 27, 2023 Category: Biochemistry Authors: Paula Sienes Bailo Nuria Go ñi Ros B árbara Menéndez Jándula Ramiro Álvarez Alegret Eduardo Gonz ález Gómez Ricardo Gonz ález Tarancón Silvia Izquierdo Álvarez Source Type: research