Constitutional Mosaic Pericentromeric Trisomy 8 in a Female Patient With Aplastic Anemia

Area of Science:

• Genetics
• Hematology
• Oncology

Background:

• Aplastic anemia involves pancytopenia and bone marrow hypoplasia, with acquired cytogenetic abnormalities like trisomy 8 in 4-15% of cases.
• Constitutional mosaic trisomy 8 increases risks for cytopenia and myeloid malignancies, while specific duplications (8p11.21q11.21) are linked to developmental issues and hematologic disorders.

Observation:

• A 19-year-old female presented with menorrhagia, vitamin B12 deficiency, short stature, pancytopenia, and bone marrow aplasia.
• G-banded chromosome and FISH analyses confirmed constitutional mosaic pericentromeric trisomy 8.
• Chromosomal microarray identified mosaic duplications in the 8p12q11.21 region, encompassing 51 OMIM genes, including 16 morbid genes and 9 with autosomal dominant inheritance.

Findings:

• Several genes within the duplicated 8p12q11.21 region, including FGFR1, ASH2L, ANK1, KAT6A, IKBKB, PLAT, and CEBPD, are implicated in hematologic disorders.
• FGFR1, ASH2L, KAT6A, and IKBKB showed significant triplosensitivity scores.
• Overlap with 13 previously reported cases revealed three with hematologic disorders (neutropenia, juvenile myelomonocytic leukemia).

Implications:

• The 8p12q11.21 region is a potential causal region for aplastic anemia.
• This case emphasizes the need for ongoing monitoring of the patient for potential progression to hematologic malignancy.
• Further research into this specific chromosomal region is warranted to understand its role in hematologic disorders.