Melkoniemi Miia, Koillinen Hannele, Männikkö Minna, Warman Matthew L, Pihlajamaa Tero, Kääriäinen Helena, Rautio Jorma, Hukki Jyri, Stofko Joseph A, Cisneros George J, Krakow Deborah, Cohn Daniel H, Kere Juha, Ala-Kokko Leena
Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland.
Eur J Hum Genet. 2003 Mar;11(3):265-70. doi: 10.1038/sj.ejhg.5200950.
Cleft palate is a common birth defect, but its etiopathogenesis is mostly unknown. Several studies have shown that cleft palate has a strong genetic component. Robin sequence consists of three of the following four findings: micrognathia, glossoptosis, obstructive apnea, and cleft palate. While cleft palate is mainly nonsyndromic, about 80 percent of Robin sequence cases are associated with syndromes. Mutations in genes coding for cartilage collagens II and XI, COL2A1, COL11A1 and COL11A2, have been shown to cause chondrodysplasias that are commonly associated with Robin sequence, micrognathia or cleft palate. We therefore analyzed a cohort of 24 patients with nonsyndromic Robin sequence, 17 with nonsyndromic cleft palate and 21 with nonsyndromic micrognathia for mutations in COL11A2. A total of 23 Robin sequence patients were also analyzed for mutations in COL2A1 and COL11A1. We detected two disease-associated mutations in patients with Robin sequence, an Arg to stop codon mutation in COL11A2 and a splicing mutation in COL11A1. Two putatively disease-associated sequence variations were found in COL11A1 in Robin sequence patients, one in COL11A2 in a patient with micrognathia and one in COL2A1 in two patients with Robin sequence. The results showed that sequence variations in these genes can play a role in the etiology of Robin sequence, cleft palate and micrognathia but are not common causes of these phenotypes.
腭裂是一种常见的出生缺陷，但其发病机制大多不明。多项研究表明，腭裂具有很强的遗传因素。罗宾序列由以下四项发现中的三项组成：小颌畸形、舌后坠、阻塞性呼吸暂停和腭裂。虽然腭裂主要是非综合征性的，但约80%的罗宾序列病例与综合征有关。编码软骨胶原蛋白II和XI的基因COL2A1、COL11A1和COL11A2中的突变已被证明会导致软骨发育异常，这些异常通常与罗宾序列、小颌畸形或腭裂有关。因此，我们分析了一组24例非综合征性罗宾序列患者、17例非综合征性腭裂患者和21例非综合征性小颌畸形患者的COL11A2突变情况。还对总共23例罗宾序列患者的COL2A1和COL11A1突变进行了分析。我们在罗宾序列患者中检测到两个与疾病相关的突变，一个是COL11A2中从精氨酸到终止密码子的突变，另一个是COL11A1中的剪接突变。在罗宾序列患者的COL11A1中发现了两个可能与疾病相关的序列变异，在一名小颌畸形患者的COL11A2中发现了一个，在两名罗宾序列患者的COL2A1中发现了一个。结果表明，这些基因中的序列变异可能在罗宾序列、腭裂和小颌畸形的病因中起作用，但不是这些表型的常见原因。
