Khan Aneal, Hyde R Katherine, Dutra Amalia, Mohide Patrick, Liu Paul
Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada.
Am J Med Genet A. 2006 Nov 1;140(21):2349-54. doi: 10.1002/ajmg.a.31479.
The core binding factor beta gene (CBFB), essential to bone morphogenesis, is located at 16q22.1. Homozygous deficiency of CBFB leads to ossification defects in mice. CBFB forms a heterodimer with RUNX2 (CBFA1) during embryonic bone development. RUNX2 mutations lead to cleidocranial dysplasia in humans. We describe an infant boy with an interstitial deletion of 16q21q22, delayed skull ossification, cleft palate, and heart anomalies who had a difficult course in infancy but eventually improved and is healthy. He was found to have CBFB haploinsufficiency, but did not have mutations in RUNX2. We suggest that 16q21q22 deletion be considered when there are antenatal or postnatal findings of enlarged cranial sutures with or without cleft palate. The finding of CBFB haploinsufficiency in our case and the similarity of cranial ossification defects with a mouse model of CBFB deletion suggest a role for CBFB in cranial bone development in humans.
核心结合因子β基因（CBFB）对骨形态发生至关重要，位于16q22.1。CBFB基因纯合缺失会导致小鼠出现骨化缺陷。在胚胎骨发育过程中，CBFB与RUNX2（CBFA1）形成异源二聚体。RUNX2突变会导致人类锁骨颅骨发育不全。我们描述了一名患有16q21q22间质性缺失、颅骨骨化延迟、腭裂和心脏异常的男婴，其婴儿期病情复杂，但最终有所改善且身体健康。他被发现存在CBFB单倍体不足，但RUNX2没有突变。我们建议，当产前或产后发现有或无腭裂的颅缝增宽时，应考虑16q21q22缺失。我们病例中CBFB单倍体不足的发现以及颅骨骨化缺陷与CBFB缺失小鼠模型的相似性表明，CBFB在人类颅骨发育中起作用。
