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<p>Wiedemann-Steiner syndrome (WSS) is a congenital malformation syndrome characterized by intellectual disability, developmental delay, and distinctive facial features, caused by germline mutations in the <i>KMT2A</i> gene. Despite the key role of <i>KMT2A</i> in hematopoiesis, leukemia has not been previously reported in WSS patients. This report presents the first documented case of acute lymphoblastic leukemia (ALL) in a WSS patient. A 16-year-old boy with developmental delay, distinct facial features, and genital abnormalities was diagnosed with WSS following the identification of a heterozygous frameshift mutation in <i>KMT2A</i>. At age 17, he developed T-cell ALL harboring the <i>KMT2A-CBL</i> fusion gene, of which only nine cases have been reported so far. cDNA sequence analysis of the <i>KMT2A-CBL</i> transcript at the site of the germline <i>KMT2A</i> pathogenic variant revealed a wild-type sequence, indicating that the <i>KMT2A-CBL</i> fusion occurred on the wild-type allele. While this observation suggests a potential cooperative role of the <i>KMT2A</i>-<i>CBL</i> chimeric gene and the germline <i>KMT2A</i> pathogenic mutation in leukemogenesis, the rarity of leukemia in WSS underscores the need for cautious interpretation. This case provides preliminary insights into a possible mechanism of leukemogenesis in WSS, but further studies are required to clarify the relationship between WSS and ALL.</p>

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KMT2A-CBL fusion gene in the first reported case of T-cell acute lymphoblastic leukemia associated with Wiedemann-Steiner syndrome

  • 期刊论文

  • 发表日期：

    2025年3月28日

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  • Akihiro Nishimura,
  • Akihiro Tamura,
  • Tomoko Fujikawa,
  • Shotaro Inoue,
  • Naoko Nakatani,
  • Kandai Nozu,
  • Nobuyuki Yamamoto

摘要

Wiedemann-Steiner syndrome (WSS) is a congenital malformation syndrome characterized by intellectual disability, developmental delay, and distinctive facial features, caused by germline mutations in the KMT2A gene. Despite the key role of KMT2A in hematopoiesis, leukemia has not been previously reported in WSS patients. This report presents the first documented case of acute lymphoblastic leukemia (ALL) in a WSS patient. A 16-year-old boy with developmental delay, distinct facial features, and genital abnormalities was diagnosed with WSS following the identification of a heterozygous frameshift mutation in KMT2A. At age 17, he developed T-cell ALL harboring the KMT2A-CBL fusion gene, of which only nine cases have been reported so far. cDNA sequence analysis of the KMT2A-CBL transcript at the site of the germline KMT2A pathogenic variant revealed a wild-type sequence, indicating that the KMT2A-CBL fusion occurred on the wild-type allele. While this observation suggests a potential cooperative role of the KMT2A-CBL chimeric gene and the germline KMT2A pathogenic mutation in leukemogenesis, the rarity of leukemia in WSS underscores the need for cautious interpretation. This case provides preliminary insights into a possible mechanism of leukemogenesis in WSS, but further studies are required to clarify the relationship between WSS and ALL.