Inheritance of cleft palate in Italy. Evidence for a major autosomal recessive locus
Inheritance of cleft palate in Italy. Evidence for a major autosomal recessive locus
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DOI：
10.1007/s004390050491
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发表时间：
1997-08-01
期刊：
影响因子：
5.3
通讯作者：
Milan, M
中科院分区：
文献类型：
--
作者：
Clementi, M;Tenconi, R;Milan, M
虽然一些研究已经证明了非综合征性腭裂（CP）的家族聚集性，但其遗传方式仍然不确定。我们报告了在357个连续的非综合征型CP新生儿（即，CP不是畸形综合征、序列或关联的组成特征）。并于1981-1993年期间在意大利东北部和Emilia Romagna先天性畸形登记处登记。这个样本基于大量的连续出生。在明确界定的地理区域内，通过质量控制来检测相关的异常和畸形综合征。是独立的受影响的主题在家庭和CP的严重程度，健身，和生存的数量。我们用混合模型进行了分析。非综合征性CP的整个样品，包括分离的（即，无其他异常）CP（CPI）和CP伴至少一种其他异常（CPA），不可能诊断为畸形综合征。当非综合征CP（包括CPA）被认为是在分析中，有CPA和CPI之间没有异质性，也没有CP包括硬腭（CPH）和CP的软腭（CPS）之间。POINTER和COMDS程序不能区分不同的遗传模型：只有非遗传传播的假设被拒绝。COMDS分析双位点模型。这表明修饰基因座（或多个修饰基因座）除了单个主基因座（SML）之外还起作用，没有显示出比SML、多基因和多因子模型更好的拟合证据。当添加严重性参数（定义为CPH和CPS）时，CPI和CPA显示出异质性。最后，当分析仅限于CPI并包括严重程度信息时，具有低突变率和决定性CPH的隐性SML提供了显著的最佳拟合。定义CPI的遗传模型并提供SML遗传的证据表明可以实施遗传连锁研究。这一结论与先前的研究一致，这些研究表明，仅在人类中转化生长因子α和CP的等位基因之间存在显著关联。单隐性基因可能在小鼠和布列塔尼犬的腭发育过程中起关键作用。将候选基因应用于人类CPH家族可以揭示这些基因是否参与。
Although several studies have demonstrated familial aggregation of nonsyndromic cleft palate (CP), the mode of inheritance still remains uncertain. We report the results of complex segregation analysis performed in families of 357 consecutive newborns affected with nonsyndromic CP (i.e., CP not a component feature of malformation syndrome, sequence or association). and registered in the North East Italy and Emilia Romagna congenital malformation registries in the period 1981-1993. This sample. based on a large number of consecutive births. in a well-defined geographical area, with quality control to detect associated anomalies and malformation syndromes. is independent of the number of affected subjects in the family and of CP severity, fitness, and survival. We have analyzed, using the mixed model. the whole sample of nonsyndromic CP, including isolated (i.e., without other anomalies) CP (CPI) and CP associated with at least one other anomaly (CPA), for which a diagnosis of malformation syndrome was not possible. When nonsyndromic CP (including CPA) are considered in the analysis, there is no heterogeneity between CPA and CPI nor between CP including hard palate (CPH) and CP of the soft palate only (CPS). POINTER and COMDS programs cannot discriminate between alternative genetic models: only the hypothesis of non-genetic transmission is rejected. The COMDS analysis two-locus model. which indicates that a modifier locus (or loci) operates in addition to a single major locus (SML), does not show evidence of better fit than SML, polygenic, and multifactorial models, When the severity parameter (defined as CPH and CPS) is added, CPI and CPA show heterogeneity. Eventually, when the analysis is limited to CPI and includes information on severity, a recessive SML, with low penetrance and determining CPH, provides a significant best fit. To have defined a genetic model for CPI and provided evidence for SML inheritance suggests that genetic linkage studies could be implemented. This conclusion is in agreement with previous studies which showed a significant association between alleles of transforming growth factor alpha and CP only in humans. and that single recessive genes may play a crucial role during palatogenesis in mice as well as in Brittany spaniels. Application of the candidate genes to human CPH families could reveal whether these genes are involved.