Fonseca Renata F, de Carvalho Flávia M, Poletta Fernando A, Montaner David, Dopazo Joaquin, Mereb Juan C, Moreira Miguel A M, Seuanez Hector N, Vieira Alexandre R, Castilla Eduardo E, Orioli Iêda M
Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
ECLAMC (Latin-American Collaborative Study of Congenital Malformations) at INAGEMP (National Institute of Population Medical Genetics), Rio de Janeiro, Brazil.
Eur J Oral Sci. 2015 Oct;123(5):381-384. doi: 10.1111/eos.12212. Epub 2015 Sep 1.
The etiology of cleft lip with or without cleft palate (CL±P) is complex and heterogeneous, and multiple genetic and environmental factors are involved. Some candidate genes reported to be associated with oral clefts are located on the X chromosome. At least three genes causing X-linked syndromes [midline 1 (MID1), oral-facial-digital syndrome 1 (OFD1), and dystrophin (DMD)] were previously found to be associated with isolated CL±P. We attempted to confirm the role of X-linked genes in the etiology of isolated CL±P in a South American population through a family-based genome-wide scan. We studied 27 affected children and their mothers, from 26 families, in a Patagonian population with a high prevalence of CL±P. We conducted an exploratory analysis of the X chromosome to identify candidate regions associated with CL±P. Four genomic segments were identified, two of which showed a statistically significant association with CL±P. One is an 11-kb region of Xp21.1 containing the DMD gene, and the other is an intergenic region (8.7 kb; Xp11.4). Our results are consistent with recent data on the involvement of the DMD gene in the etiology of CL±P. The MID1 and OFD1 genes were not included in the four potential CL±P-associated X-chromosome genomic segments.
唇裂伴或不伴腭裂（CL±P）的病因复杂且具有异质性，涉及多种遗传和环境因素。一些据报道与口腔裂隙相关的候选基因位于X染色体上。先前发现至少三个导致X连锁综合征的基因[中线1（MID1）、口面指综合征1（OFD1）和肌营养不良蛋白（DMD）]与孤立性CL±P相关。我们试图通过基于家系的全基因组扫描来证实X连锁基因在南美人群孤立性CL±P病因中的作用。我们研究了来自26个家庭的27名患病儿童及其母亲，这些家庭来自巴塔哥尼亚地区，该地区CL±P患病率较高。我们对X染色体进行了探索性分析，以确定与CL±P相关的候选区域。共识别出四个基因组片段，其中两个与CL±P显示出统计学上的显著关联。一个是位于Xp21.1的包含DMD基因的11kb区域，另一个是基因间区域（8.7kb；Xp11.4）。我们的结果与最近关于DMD基因参与CL±P病因的研究数据一致。MID1和OFD1基因未包含在四个潜在的与CL±P相关的X染色体基因组片段中。
