NOVEL MALIGNANT T-CELL AMPLIFIED SEQUENCE 1 (MCTS1) MUTATION RESULTING IN MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE

A 24-year-old male with disseminated Mycobacteria abscessus infection was found to have a novel MCTS1 mutation [c.178del p.(Glu60LysfsTer5)] on whole exome sequencing (WES), resulting in a premature stop signal in the MCTS1 gene. This case features a novel presentation of MCTS1 deficiency and highlights the role of WES in diagnosis and treatment based on molecular mechanism. A 24-year-old male presented with weight loss and diarrhea that started as an adolescent. At 22, he was found to have bulky intra-abdominal lymphadenopathy. Cultures from an excisional lymph node biopsy grew Mycobacterium abscessus subspp abscessus (MABc). His disseminated MABc infection raised concern for an inborn error of immunity (IEI). His immune labs showed hypergammaglobulinemia but were otherwise unremarkable. An Invitae targeted 429 gene panel was similarly unrevealing. WES identified a de novo hemizygous pathogenic MCTS1 variant that is thought to impair JAK2 translation in T lymphocytes , decreasing the IL-23-dependent production of IFNγ. Despite being on a multi-drug antibiotic regimen, he continued to have weight loss and diarrhea. Based on knowledge of his immune defect, we initiated treatment with subcutaneous IFNγ. X-linked recessive MCTS1 deficiency was first linked to MSMD in 2023. A small cohort of MCTS1-deficient patients has been reported, who all presented in infancy with complications from the BCG vaccine. Our patient is the first reported case of non-BCG MSMD associated with MCTS1 deficiency. This case illustrates the importance of pursuing WES to evaluate newly described genes in patients whose presentation is highly suspicious for an IEI.