Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013, Seville, Spain.
J Mol Med (Berl). 2010 May;88(5):507-14. doi: 10.1007/s00109-010-0592-7. Epub 2010 Feb 4.
SOX10 protein is a key transcription factor during neural crest development. Mutations in SOX10 are associated with several neurocristopathies such as Waardenburg syndrome type IV (WS4), a congenital disorder characterized by the association of hearing loss, pigmentary abnormalities, and absence of ganglion cells in the myenteric and submucosal plexus of the gastrointestinal tract, also known as aganglionic megacolon or Hirschsprung disease (HSCR). Several mutations at this locus are known to cause a high percentage of WS4 cases, but no SOX10 mutations had been ever reported associated to isolated HSCR patient. Therefore, nonsyndromic HSCR was initially thought not to be associated to mutations at this particular locus. In the present study, we describe the evaluation of the SOX10 gene in a series of 196 isolated HSCR cases, the largest patient series evaluated so far, and report a truncating c.153-155del mutation. This is the first time that a SOX10 mutation is detected in an isolated HSCR patient, which completely changes the scenario for the implications of SOX10 mutations in human disease, giving us a new tool for genetic counseling.
SOX10 蛋白是神经嵴发育过程中的关键转录因子。SOX10 突变与几种神经嵴病变有关，例如 Waardenburg 综合征 IV 型（WS4），这是一种先天性疾病，其特征是听力损失、色素异常以及胃肠道肌间和黏膜下神经丛的神经节细胞缺失，也称为无神经节性巨结肠或先天性巨结肠（HSCR）。该基因座的几个突变已知会导致很大比例的 WS4 病例，但从未报道过与孤立性 HSCR 患者相关的 SOX10 突变。因此，最初认为非综合征性 HSCR 与该特定基因座的突变无关。在本研究中，我们评估了 SOX10 基因在 196 例孤立性 HSCR 病例中的情况，这是迄今为止评估的最大的患者系列，并报告了一个截断性 c.153-155del 突变。这是首次在孤立性 HSCR 患者中检测到 SOX10 突变，这完全改变了 SOX10 突变在人类疾病中的意义，为我们提供了遗传咨询的新工具。
