Mostowska Adrianna, Biedziak Barbara, Trzeciak Wieslaw H
Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznan, Poland.
Eur J Hum Genet. 2006 Feb;14(2):173-9. doi: 10.1038/sj.ejhg.5201536.
PAX9 is a paired domain transcription factor that plays a critical role in odontogenesis. All mutations of PAX9 identified to date have been associated with nonsyndromic form of tooth agenesis. The present report describes an unusual novel mutation in PAX9 identified in a family with severe molar oligodontia. This heterozygous deletion combined with 24 bp insertion (including a 5' splice site) is localized in the second exon beyond the highly conserved paired box sequence, and might result either in a premature termination of translation at aa 210 or in an aberrant splicing, leading to a frameshift and premature termination of translation at aa 314. Real-time PCR analysis revealed no mutated transcript in cultured lymphocytes of one of the affected individuals indicating that the novel mutation might result in rapid degradation of the mutated transcript leading to haploinsufficiency of PAX9. Our results support the view that mutations in PAX9 constitute a causative factor in nonsyndromic oligodontia.
PAX9是一种配对结构域转录因子，在牙齿发育过程中起关键作用。迄今为止鉴定出的所有PAX9突变均与非综合征型牙齿发育不全有关。本报告描述了在一个患有严重磨牙少牙症的家族中鉴定出的PAX9一种不寻常的新突变。这种杂合缺失与24 bp插入（包括一个5'剪接位点）相结合，位于高度保守的配对盒序列之外的第二个外显子中，可能导致在第210位氨基酸处翻译提前终止，或导致异常剪接，从而导致移码并在第314位氨基酸处翻译提前终止。实时PCR分析显示，其中一名受影响个体的培养淋巴细胞中未检测到突变转录本，这表明该新突变可能导致突变转录本快速降解，从而导致PAX9单倍体不足。我们的结果支持以下观点：PAX9突变是非综合征型少牙症的一个致病因素。
