PMID- 35371815
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220405
IS  - 2168-8184 (Print)
IS  - 2168-8184 (Electronic)
IS  - 2168-8184 (Linking)
VI  - 14
IP  - 2
DP  - 2022 Feb
TI  - A Case of Aplastic Anemia and Colon Cancer With Underlying Spliceosome Mutation: 
      Is It an Incidental Finding or a Novel Association?
PG  - e22632
LID - 10.7759/cureus.22632 [doi]
LID - e22632
AB  - Alternative splicing is an epigenetic mechanism that plays a role in the 
      development and function of antigen-specific lymphocytes. One such is the 
      zinc-finger-RNA-binding-motif-and-serine/arginine-rich-2 (ZRSR2), which is 
      clinically implicated in myelodysplastic syndrome and leukemia. Here, we present 
      a case of a young male with myriad autoimmune conditions and adenocarcinoma of 
      the colon in the setting of ZRSR2 mutation. A 28-year-old male with common 
      variable immunodeficiency disease, atopic dermatitis, autoimmune 
      gastroenteropathy, inflammatory polyarthropathy, primary bone marrow failure, 
      colon cancer, and family history of Lynch syndrome was admitted to our hospital 
      for an acute flare of autoimmune enteropathy secondary to subtherapeutic 
      tacrolimus levels. He initially developed pancytopenia at the age of 26 years. 
      Workup for HIV, hepatitis, cytomegalovirus, human-herpesvirus 6, parvovirus was 
      negative. Partial thromboplastin time (PTT), international normalized ratio 
      (INR), d-dimer, ferritin, iron profile, antinuclear antibodies (ANA) screen was 
      unremarkable. Direct, indirect, and super-combs antibodies were undetectable. 
      Chromosomal study for Fanconi-related chromosomal breakage and telomerase gene 
      panel was negative. Flow cytometry did not reveal an abnormal clone. Bone marrow 
      biopsy showed markedly hypocellular marrow with reduced trilineage hematopoiesis 
      and 1% blasts with normal cytogenetics, immunohistochemistry, fluorescence in 
      situ hybridization (FISH), and negative for myelodysplastic syndrome 
      and paroxysmal nocturnal hemoglobinuria (PNH). Cincinnati inherited children's 
      bone marrow transplant (BMT) panel was negative. He was diagnosed with aplastic 
      anemia and was treated with antithymocyte globulin, cyclosporine, prednisone, and 
      currently tacrolimus. At the age of 26 years, he was diagnosed with colon 
      cancer. Immunohistochemistry was positive for MLH1, but the confirmatory genetic 
      testing for Lynch syndrome was negative. He underwent total proctocolectomy and 
      ileostomy and is currently in remission. Next-generation sequencing of bone 
      marrow revealed a germline homozygous ZRSR2 mutation.  ZRSR2 spliceosome 
      mutations are more common in males as it's an X-linked gene. They are seen in 
      myelodysplastic syndrome, leukemia, increased autoimmune phenomenon, and 35 cases 
      of colon cancer associated with this mutation are reported. In the setting of 
      aplastic anemia and lynch negative colon cancer, we suspect our patient could 
      have aplastic anemia due to an autoimmune phenomenon, underlying common variable 
      immunodeficiency disease (CVID), or the new ZRSR2 mutation could be playing a 
      role. Further studies and research is warranted to determine its true association 
      with the disease entities. The underlying contributing factor is ZRSR2 mutation.
CI  - Copyright (c) 2022, Thurlapati et al.
FAU - Thurlapati, Aswani
AU  - Thurlapati A
AD  - Internal Medicine, Louisiana State University (LSU) Health, Shreveport, USA.
FAU - Boudreaux, Kyle
AU  - Boudreaux K
AD  - Internal Medicine, Louisiana State University (LSU) Health, Shreveport, USA.
FAU - Guntupalli, Srinandan
AU  - Guntupalli S
AD  - Hematology and Oncology, Louisiana State University (LSU) Health, Shreveport, 
      USA.
FAU - Mansour, Richard P
AU  - Mansour RP
AD  - Hematology and Oncology, Louisiana State University (LSU) Health, Shreveport, 
      USA.
FAU - Bhayani, Shahzeem
AU  - Bhayani S
AD  - Internal Medicine, Louisiana State University (LSU) Health, Shreveport, USA.
LA  - eng
PT  - Case Reports
DEP - 20220226
PL  - United States
TA  - Cureus
JT  - Cureus
JID - 101596737
PMC - PMC8960534
OTO - NOTNLM
OT  - alternative splicing
OT  - aplastic anemia
OT  - colon cancer
OT  - spliceosome mutation
OT  - zrsr2 mutation
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/04/05 06:00
MHDA- 2022/04/05 06:01
PMCR- 2022/02/26
CRDT- 2022/04/04 05:31
PHST- 2022/02/24 00:00 [accepted]
PHST- 2022/04/04 05:31 [entrez]
PHST- 2022/04/05 06:00 [pubmed]
PHST- 2022/04/05 06:01 [medline]
PHST- 2022/02/26 00:00 [pmc-release]
AID - 10.7759/cureus.22632 [doi]
PST - epublish
SO  - Cureus. 2022 Feb 26;14(2):e22632. doi: 10.7759/cureus.22632. eCollection 2022 
      Feb.