Warrington A, Vieira A R, Christensen K, Orioli I M, Castilla E E, Romitti P A, Murray J C
J Med Genet. 2006 Jun;43(6):e26. doi: 10.1136/jmg.2005.034785.
Clefts of the lip and palate are common birth defects, affecting approximately 1 in 700 births worldwide. The aetiology of clefting is complex, with multiple genetic and environmental influences.
Genotype based linkage disequilibrium analysis was conducted using the family based association test (FBAT) and the likelihood ratio test (LRT). We also carried out direct sequencing of the PVR and PVRL2 candidate genes based on their homology to PVRL1, a gene shown previously to cause Margarita Island clefting. Participants included 434 patients with cleft lip with or without cleft palate or cleft palate only and their mothers from eight countries in South America, 205 nuclear triads (father-mother-affected child) from Iowa, 541 nuclear triads from Denmark, and 100 patients with cleft lip and palate from the Philippines.
An allelic variant in the PVR gene showed statistically significant association with both South American and Iowa populations (p = 0.0007 and p = 0.0009, respectively). Direct sequencing of PVR and PVRL2 yielded 26 variants, including two rare amino acid changes, one in each gene, which were not seen in controls.
We found an association between a common variant in a gene at 19q and isolated clefting in two heterogeneous populations. However, it is unclear from our data if rare variants in PVR and PVRL2 are sufficient to cause clefting in isolation.
唇腭裂是常见的出生缺陷，全球约每700例出生中就有1例受影响。腭裂的病因复杂，受多种遗传和环境因素影响。
使用基于家系的关联检验（FBAT）和似然比检验（LRT）进行基于基因型的连锁不平衡分析。我们还基于PVR和PVRL2候选基因与PVRL1的同源性对其进行直接测序，PVRL1基因先前已被证明可导致玛格丽塔岛腭裂。参与者包括来自南美洲八个国家的434例唇裂伴或不伴腭裂或仅腭裂患者及其母亲、来自爱荷华州的205个核心三联体（父亲-母亲-患病子女）、来自丹麦的541个核心三联体以及来自菲律宾的100例唇腭裂患者。
PVR基因中的一个等位基因变异与南美洲和爱荷华州人群均显示出统计学上的显著关联（分别为p = 0.0007和p = 0.0009）。对PVR和PVRL2的直接测序产生了26个变异，包括两个罕见的氨基酸变化，每个基因各一个，在对照组中未发现。
我们在两个异质人群中发现19q上一个基因的常见变异与孤立性腭裂之间存在关联。然而，从我们的数据尚不清楚PVR和PVRL2中的罕见变异是否足以单独导致腭裂。
