Case Report: ETV6 c.744del gene mutation acute lymphoblastic leukemia in identical twins

It is extremely rare for monozygotic twins to both develop leukemia. This paper reports a clinical case in which a pair of monozygotic twins with germline ETV6 gene mutations successively developed acute lymphoblastic leukemia (B-cell type, ALL-B). The ETV6:c.744del (p.S248fs) is a novel germline mutation associated with familial susceptibility to hematologic malignancies. This mutation site has not been detected in relevant databases or literature, and this is the first international report of it. It provides reference value for genetic screening of such diseases.

The elder twin (2 years old) presented with fever and skin petechiae; the younger twin (4 years old) presented with knee joint pain and lymphadenopathy. Both were diagnosed with B-cell ALL. Germline ETV6 c.744del was confirmed using DNA from buccal swabs and DNA-based next-generation sequencing. The mother and maternal uncle are carriers; the father is wild-type. The younger twin carried additional somatic NF1 and KRAS mutations.

The elder twin achieved complete remission and has remained disease-free for 42 months. The younger twin relapsed during maintenance therapy and underwent allogeneic hematopoietic stem cell transplantation from their uncle (non-carrier,their father's younger brother), achieving remission.

The successive occurrence of ALL-B with germline ETV6:c.744del mutation in the twins suggests genetic susceptibility to the disease. The frameshift mutation of ETV6:c.744del may serve as a potential driving factor. It is recommended that germline genetic testing and family screening be conducted for all pediatric patients with familial clustering of leukemia.