Kimani Jane W, Shi Min, Daack-Hirsch Sandra, Christensen Kaare, Moretti-Ferreira Danilo, Marazita Mary L, Field L Leigh, Canady John W, Murray Jeffrey C
Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
Am J Med Genet A. 2007 Dec 15;143A(24):3267-72. doi: 10.1002/ajmg.a.32098.
Nonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X-linked clefting syndromes, we investigated the role of skewed X chromosome inactivation (XCI) in orofacial clefts. Our samples consisted of female monozygotic (MZ) twins (n = 8) and sister pairs (n = 152) discordant for nonsyndromic clefting. We measured the XCI pattern in peripheral blood lymphocyte DNA using a methylation based androgen receptor gene assay. Skewing of XCI was defined as the deviation in inactivation pattern from a 50:50 ratio. Our analysis revealed no significant difference in the degree of skewing between twin pairs (P = 0.3). However, borderline significant differences were observed in the sister pairs (P = 0.02), with the cleft lip with cleft palate group showing the most significant result (P = 0.01). We did not find evidence for involvement of skewed XCI in the discordance for clefting in our sample of female MZ twins. However, results from the paired sister study suggest the potential contribution of skewed XCI to orofacial clefting, particularly cleft lip and palate.
非综合征性唇裂和/或腭裂是常见的出生缺陷，具有很强的遗传成分。基于唇腭裂表型的性别比例不均衡、与X染色体连锁的证据以及几种X连锁腭裂综合征的发生情况，我们研究了X染色体失活（XCI）偏斜在口腔颌面部裂隙中的作用。我们的样本包括8对女性单卵双胞胎（MZ）和152对非综合征性唇腭裂不一致的姐妹对。我们使用基于甲基化的雄激素受体基因检测方法测量外周血淋巴细胞DNA中的XCI模式。XCI偏斜定义为失活模式偏离50:50的比例。我们的分析显示，双胞胎对之间的偏斜程度没有显著差异（P = 0.3）。然而，在姐妹对中观察到临界显著差异（P = 0.02），其中唇腭裂组显示出最显著的结果（P =0.01）。在我们的女性MZ双胞胎样本中，我们没有发现XCI偏斜参与唇腭裂不一致的证据。然而，配对姐妹研究的结果表明，XCI偏斜对口腔颌面部裂隙，特别是唇腭裂有潜在影响。
