生物谷報(bào)道：人們認(rèn)識脊柱側(cè)凸（scoliosis）的歷史能夠追溯到古希臘希波克拉底（古希臘名醫(yī)）時(shí)代，但直到今天,，脊柱側(cè)凸的病因仍舊是個(gè)謎,。最近，華盛頓大學(xué)醫(yī)學(xué)院,、德州大學(xué)西南醫(yī)學(xué)院等單位的研究人員發(fā)現(xiàn),，基因CHD7缺陷會導(dǎo)致脊柱C和S型彎曲。遺傳學(xué),、醫(yī)學(xué)和耳科學(xué)副教授Anne Bowcock說,，掌握了基因影響脊柱發(fā)育的機(jī)制,，就能理論預(yù)測胎兒脊柱側(cè)凸的可能性，提早進(jìn)行治療,。詳細(xì)內(nèi)容刊登于5月份出版的《美國人類遺傳學(xué)雜志》,。
盡管脊柱側(cè)凸有家族傾向，但研究人員一直不清楚其遺傳機(jī)制,。主要原因是這種疾病看起來像是幾種不同基因和環(huán)境共同作用的結(jié)果,。CHD7基因在許多基本的細(xì)胞功能中發(fā)揮關(guān)鍵作用。研究人員發(fā)現(xiàn)CHARGE綜合癥（一種罕見的綜合癥）患者體內(nèi),，CHD7基因缺失或發(fā)生損傷嚴(yán)重,。CHARGE綜合癥嬰兒經(jīng)常幼年夭折，即使幸存也會罹患心臟缺陷,、智力遲鈍等疾病,，并伴隨晚期的脊柱側(cè)凸。Bowcock等感覺CHD7的適度突變與其它類型的脊柱側(cè)凸有關(guān),。
Scottish Rite醫(yī)院Carol Wise博士率領(lǐng)的研究小組,，收集來自52個(gè)家庭成員中有脊柱側(cè)凸患者的家族資料?；颊呒怪鶑澢骄鶠?0度,，沒有Marfan綜合癥或大腦性麻痹等與脊柱側(cè)凸有關(guān)的其它疾病。研究人員執(zhí)行全基因組掃描,，對這些家族成員兩套染色體的60億個(gè)堿基對進(jìn)行測序并分析數(shù)據(jù),。
研究結(jié)果顯示，脊柱側(cè)凸患者的基因非編碼區(qū)有缺陷,，這意味著CHD7蛋白的生成不受影響,。研究人員推測這種特定突變會改變控制基因表達(dá)起始位點(diǎn)的分子的結(jié)合情況，進(jìn)而導(dǎo)致基因關(guān)閉頻率上升,，CHD7產(chǎn)量下降,。
遺傳學(xué)和兒科學(xué)教授Michael Lovett說，蛋白產(chǎn)量的變化很微妙,，與經(jīng)常發(fā)生的某種脊柱側(cè)凸高度相關(guān),，這種特異缺陷或許是脊柱側(cè)凸的真正或極為重要的原因。目前,，研究人員正在其他脊柱側(cè)凸家族中尋找這種疾病的其它遺傳突變,。
原始出處:
Am. J. Hum. Genet., 80:957-965, 2007
CHD7 Gene Polymorphisms Are Associated with Susceptibility to Idiopathic Scoliosis
Xiaochong Gao, Derek Gordon, Dongping Zhang, Richard Browne, Cynthia Helms, Joseph Gillum, Samuel Weber, Shonn Devroy, Saralove Swaney, Matthew Dobbs, Jose Morcuende, Val Sheffield, Michael Lovett, Anne Bowcock, John Herring, and Carol Wise
From the Seay Center for Musculoskeletal Research (X.G.; D.Z.; R.B.; J.G.; S.W.; S.D.; S.S.; C.W.), Orthopaedics, Texas Scottish Rite Hospital (J.H.), and Department of Orthopaedic Surgery (J.H.; C.W.) and McDermott Center for Human Growth and Development (C.W.), University of Texas Southwestern Medical Center, Dallas; Department of Genetics, Rutgers, The State University of New Jersey, Piscataway (D.G.); Departments of Genetics (C.H.; M.L.; A.B.) and Orthopaedic Surgery (M.D.), Washington University School of Medicine, St. Louis; and Departments of Orthopaedic Surgery and Rehabilitation (J.M.) and Pediatrics (V.S.), University of Iowa School of Medicine, Iowa City
Received November 3, 2006; accepted for publication February 6, 2007; electronically published March 12, 2007.
Idiopathic scoliosis (IS) is the most common spinal deformity in children, and its etiology is unknown. To refine the search for genes underlying IS susceptibility, we ascertained a new cohort of 52 families and conducted a follow-up study of genomewide scans that produced evidence of linkage and association with 8q12 loci (multipoint LOD 2.77; P = .0028). Further fine mapping in the region revealed significant evidence of disease-associated haplotypes (P < 1.0 × 10-4) centering over exons 2–4 of the CHD7 gene associated with the CHARGE (coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness) syndrome of multiple developmental anomalies. Resequencing CHD7 exons and conserved intronic sequence blocks excluded coding changes but revealed at least one potentially functional polymorphism that is overtransmitted (P = .005) to affected offspring and predicts disruption of a caudal-type (cdx) transcription-factor binding site. Our results identify the first gene associated with IS susceptibility and suggest etiological overlap between the rare, early-onset CHARGE syndrome and common, later-onset IS.
