CLINICAL AND MOLECULAR GENETIC STUDY ON CLEFT LIP AND/OR CLEFT PALATE PATIENTS IN JAPAN

唇裂和/或腭裂（CL/P）是常见的颅面出生缺陷之一，影响1/500的日本人。据认为，大多数非综合征性CL/P病例是由多因素阈值模型描述的遗传和环境因素相结合引起的。近年来，主要基因座模型通过复杂分离分析最好地解释了在白人家庭中观察到的CL/P复发，许多其他小组正在试图确定负责这种疾病的主要基因座。在1989年，Arginger等报道了转化生长因子α的限制性片段长度多态性（RFLP）之间的显著关联。（TGF α）基因座与裂型发生的关系，提示TGF α基因本身或邻近区域的DNA序列与部分CL/P病例的发生有关。我们对59名非综合征CL/P患者进行了详细的细胞遗传学分析，采用高分辨显带技术和关联研究，比较了30名无血缘关系的裂骨患者和34名对照者TGF α基因座的遗传变异。总之，我们没有发现任何特定的染色体异常和TGF α和CL/P的RFLPs之间的显着关联，通过以前的研究确定的白人CL/P患者。

Cleft lip and/or cleft palate (CL/P) is one of the frequent craniofacial birth defects, affecting 1/500 Japanese. It has been suggested that most cases of nonsyndromic CL/P are caused by the combination of genetic and environmental factors as described by the multifactorial threshold model. Recently, the major locus model best explains the observed recurrence of CL/P in Caucasian families by complex segregation analysis and many other groups are trying to identifiy the major locus responsible for this disorder. In 1989, Arginger et al.reported a significant association was observed between restriction fragment length polymorphisms (RFLP) at transforming growth factor alpha (TGFalpha) locus and the occurence of clefting, suggesting that either the TGF alpha gene itself or DNA sequence in an adjacent region contribute to the development of a portion of cases of CL/P.In this study, we performed detailed cytogenetic analysis of 59 nonsyndromic CL/P patients using high resolusion banding technique and association study comparing genetic variation at TGF alpha loci in 30 unrelated clefted individuals with 34 controls. In conclusion, we could not find any specific chromosomal abnormalities and significant association between RFLPs of TGF alpha and CL/P determined by the previous studies for Caucasian CL/P patient.