Department of Oral Biology and Center for Craniofacial and Dental Genetics, University of Pittsburgh, 614 Salk Hall, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
J Dent Res. 2010 Sep;89(9):927-32. doi: 10.1177/0022034510370004. Epub 2010 May 28.
Cleft lip/palate is a defect of craniofacial development. In previous reports, chromosome 6q has been suggested as a candidate region for cleft lip/palate. A multipoint posterior probability of linkage analysis of multiplex families from the Philippines attributed an 88% probability of harboring a cleft-susceptibility gene to a narrower region on bands 6q14.2-14.3. We genotyped 2732 individuals from families and unrelated individuals with and without clefts to investigate the existence of possible cleft-susceptibility genes in this region. We found association of PRSS35 and SNAP91 genes with cleft lip/palate in the case-control cohort and in Caucasian families. Haplotype analyses support the individual associations with PRSS35. We found Prss35 expression in the head and palate of mouse embryos at critical stages for palatogenesis, whereas Snap91 was expressed in the adult brain. We provide further evidence of the involvement of chromosome 6q in cleft lip/palate and suggest PRSS35 as a novel candidate gene.
唇腭裂是一种颅面发育缺陷。在之前的报告中，6 号染色体已被提议为唇腭裂的候选区域。菲律宾的多例家系进行的多点后验概率连锁分析将 88%的携带易感性基因的概率归因于 6q14.2-14.3 带的更窄区域。我们对有或没有唇腭裂的家系和无关个体的 2732 个人进行了基因分型，以研究该区域是否存在可能的易感性基因。我们发现 PRSS35 和 SNAP91 基因与病例对照队列和高加索家系中的唇腭裂有关。单体型分析支持 PRSS35 的个体关联。我们在腭形成的关键阶段发现了 Prss35 在小鼠胚胎头部和腭中的表达，而 Snap91 在成年大脑中表达。我们提供了进一步的证据表明 6 号染色体参与了唇腭裂，并提出 PRSS35 作为一个新的候选基因。
