ピエール・ロバンあるいはロビン症候群とゲノム

「ピエール・ロバンあるいはロビン症候群とゲノム変異」という論文が出ている。最近増えてきたのがゲノムレベルのmicrodeletionやtranslocationがゲノム改変やあるいは発現調節因子の増強（あるいは減弱）をもたらす結果病因に結びつくというものである。昨年（一昨年？）は自閉症がmicrodeletionによるのだという論文が話題になっていたが、これはどちらかというと整形あるいは神経内科あるいは小児外科なんだろう。あたしらには麻酔がかけにくい患者さんのイメージしかありませんが。

ボクはアブストラクトしか読めないが、部位特異的にこの効果が現れる機序が解説してあったら面白いなあ。だってこの変化は普通に考えればsomaticでしょう。なぜ頸や口腔に発生学的に効いてくるのか、解説してあったら真に面白いと思うな。誰か読んでボクに教えて欲しいものだ。

Nature Genetics 41, 359 - 364 (2009)
Published online: 22 February 2009 |

Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence

Sabina Benko^1,14, Judy A Fantes^2,14, Jeanne Amiel^1,3, Dirk-Jan Kleinjan², Sophie Thomas¹, Jacqueline Ramsay², Negar Jamshidi⁴, Abdelkader Essafi², Simon Heaney², Christopher T Gordon⁴, David McBride², Christelle Golzio¹, Malcolm Fisher², Paul Perry², Véronique Abadie^5,6, Carmen Ayuso⁷, Muriel Holder-Espinasse⁸, Nicky Kilpatrick⁴, Melissa M Lees⁹, Arnaud Picard^10,11, I Karen Temple¹², Paul Thomas⁴, Marie-Paule Vazquez^10,11, Michel Vekemans^1,3,5, Hugues Roest Crollius¹³, Nicholas D Hastie², Arnold Munnich^1,3,5, Heather C Etchevers¹, Anna Pelet¹, Peter G Farlie⁴, David R FitzPatrick^2,14 & Stanislas Lyonnet^1,3,5,14

Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06–1.23 Mb upstream of SOX9, and microdeletions both 1.5 Mb centromeric and 1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.