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<p>There have been several reports on heterozygous loss of function variants in <i>PBX1</i> associated with congenital anomalies of the kidney and urinary tract (CAKUT). We report three patients harboring de novo heterozygous missense variants in <i>PBX1</i>, who did not have CAKUT, but instead presented with respiratory failure, developmental delay, and, the most important, a unique skeletal phenotype characterized by broad and short clavicles with coracoclavicular ankylosis and broad ischia with premature fusion of the ischiopubic synchondrosis. All the variants are clustered at the last portion of the homeobox domain. This phenotype is consistent with mouse models with functional dysregulation in Pbx1 or its interacting factor, Emx2. This study highlights a previously not reported phenotype affecting the clavicles and ischia due to <i>PBX1</i> variants and expands the clinical spectrum of <i>PBX1</i>-related disorders.</p>

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Missense variants in homeobox domain of PBX1 cause coracoclavicular ankylosis

  • 期刊论文

  • 发表日期：

    2025年10月29日

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  • Maki Iwai,
  • Kyra E. Stuurman,
  • Kirsten Meagher,
  • Lise A. Leveille,
  • Takashi Saisu,
  • Satomi Mori,
  • Tatsuro Kumaki,
  • Yumi Enomoto,
  • Noriko Aida,
  • Hisato Suzuki,
  • Toshiki Takenouchi,
  • Kenjiro Kosaki,
  • Millan S. Patel,
  • Kenji Kurosawa,
  • Gen Nishimura

摘要

There have been several reports on heterozygous loss of function variants in PBX1 associated with congenital anomalies of the kidney and urinary tract (CAKUT). We report three patients harboring de novo heterozygous missense variants in PBX1, who did not have CAKUT, but instead presented with respiratory failure, developmental delay, and, the most important, a unique skeletal phenotype characterized by broad and short clavicles with coracoclavicular ankylosis and broad ischia with premature fusion of the ischiopubic synchondrosis. All the variants are clustered at the last portion of the homeobox domain. This phenotype is consistent with mouse models with functional dysregulation in Pbx1 or its interacting factor, Emx2. This study highlights a previously not reported phenotype affecting the clavicles and ischia due to PBX1 variants and expands the clinical spectrum of PBX1-related disorders.