A case of Bloom syndrome manifesting with therapy-related myelodysplastic syndromes harboring a novel BLM gene variant.

Abstract

Bloom syndrome (BS) is an autosomal recessive genetic disorder caused by variants in the BLM gene. BS is characterized by distinct facial features, elongated limbs, and various dermatological complications including photosensitivity, poikiloderma, and telangiectatic erythema. The BLM gene encodes a RecQ helicase critical for genome maintenance, stability, and repair, and a deficiency in functional BLM protein leads to genomic instability and high predisposition to various types of cancers, particularly hematological and gastrointestinal malignancies. Here, we report a case of BS with a previously unreported variant in the BLM gene. The patient was a 34-year-old woman who presented with short stature, prominent facial features, and a history of malignancies, including lymphoma, breast cancer, and myelodysplastic syndromes (MDS). She was initially treated with azacitidine for MDS and showed transient improvement, but eventually died at age of 35 due to progression of MDS. Genetic screening revealed compound heterozygous variants in the BLM gene, with a recurrent variant previously reported in BS in one allele and a previously unreported variant in the other allele. Based on her characteristic clinical features and the presence of heterozygous variants in the BLM gene, she was diagnosed with BS harboring compound heterozygous BLM variants.

• Authors: Takuma Ohashi, Hiroyoshi Kunimoto, Jun Nukui, Haruka Teshigawara, Satoshi Koyama, Takuya Miyazaki, Maki Hagihara, Kenji Matsumoto, Eriko Koshimizu, Naomi Tsuchida, Haruka Hamanoue, Satoko Miyatake, Akihiro Yachie, Naomichi Matsumoto, Hideaki Nakajima
• Journal: International journal of hematology (Int J Hematol) Vol. 119 Issue 5 Pg. 603-607 (May 2024) ISSN: 1865-3774 [Electronic] Japan
• PMID: 38489090 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2024. Japanese Society of Hematology.

Chemical References

• RecQ Helicases
• Bloom syndrome protein
• Azacitidine

Topics

• Humans
• Bloom Syndrome (genetics)
• Female
• RecQ Helicases (genetics)
• Myelodysplastic Syndromes (genetics, drug therapy)
• Adult
• Azacitidine (adverse effects, therapeutic use)
• Fatal Outcome
• Mutation
• Heterozygote