據一項發(fā)表于10月15日American Journal of Human Genetics的研究報告,，華盛頓大學醫(yī)學院的研究人員在四個新生兒基因組中新發(fā)現一個共同的突變基因，這四個新生兒的肺部,，消化道，泌尿系統,，皮膚,，骨骼和肌肉發(fā)育異常,，并且都出現皮膚疏松(cutis laxa),。其中三名患者在在2歲之前死于呼吸衰竭,。
該基因或許對開發(fā)治療慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)有潛在影響,。
研究人員對缺失LTBP4基因的基因工程鼠進行研究,，該缺陷型小鼠的皮膚組織電鏡下也出現結締組織紊亂，與上述的其中一名新生兒癥狀相似,，并且這名新生兒同時還出現致命性肺部并發(fā)癥以及消化道和泌尿疾病。
基于上述觀察,，研究人員對LTBP4基因進行測序，證實該基因發(fā)生了突變,。
研究人員確定,，該研究是首次對這種癥狀進行報道,，因此,，課題組將這種癥狀命名為Urban-Rifkin-Davis綜合癥(Urban-Rifkin-Davis Syndrome)。（生物谷Bioon.com）
生物谷推薦原始出處：
The American Journal of Human Genetics, 15 October 2009 doi:10.1016/j.ajhg.2009.09.013
Mutations in LTBP4 Cause a Syndrome of Impaired Pulmonary, Gastrointestinal, Genitourinary, Musculoskeletal, and Dermal Development
Zsolt Urban1, 2, 3, , , Vishwanathan Hucthagowder1, Nura Schürmann1, Vesna Todorovic4, Lior Zilberberg4, Jiwon Choi6, Carla Sens1, Chester W. Brown7, 8, Robin D. Clark9, Kristen E. Holland10, Michael Marble11, 12, Lynn Y. Sakai13, Branka Dabovic4, Daniel B. Rifkin4, 5 and Elaine C. Davis6
1 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA
2 Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA
3 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
4 Department of Cell Biology, New York University Langone School of Medicine, New York, NY 10016, USA
5 Department of Medicine, New York University Langone School of Medicine, New York, NY 10016, USA
6 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada
7 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
8 Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
9 Department of Pediatrics, Loma Linda School of Medicine, Loma Linda, CA 92354, USA
10 Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
11 Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA 70118, USA
12 Children's Hospital of New Orleans, New Orleans, LA 70118, USA
13 Department of Biochemistry and Molecular Biology, Shriners Hospital for Children, Oregon Health & Science University, Portland, OR 97239, USA
We report recessive mutations in the gene for the latent transforming growth factor-β binding protein 4 (LTBP4) in four unrelated patients with a human syndrome disrupting pulmonary, gastrointestinal, urinary, musculoskeletal, craniofacial, and dermal development. All patients had severe respiratory distress, with cystic and atelectatic changes in the lungs complicated by tracheomalacia and diaphragmatic hernia. Three of the four patients died of respiratory failure. Cardiovascular lesions were mild, limited to pulmonary artery stenosis and patent foramen ovale. Gastrointestinal malformations included diverticulosis, enlargement, tortuosity, and stenosis at various levels of the intestinal tract. The urinary tract was affected by diverticulosis and hydronephrosis. Joint laxity and low muscle tone contributed to musculoskeletal problems compounded by postnatal growth delay. Craniofacial features included microretrognathia, flat midface, receding forehead, and wide fontanelles. All patients had cutis laxa. Four of the five identified LTBP4 mutations led to premature termination of translation and destabilization of the LTBP4 mRNA. Impaired synthesis and lack of deposition of LTBP4 into the extracellular matrix (ECM) caused increased transforming growth factor-β (TGF-β) activity in cultured fibroblasts and defective elastic fiber assembly in all tissues affected by the disease. These molecular defects were associated with blocked alveolarization and airway collapse in the lung. Our results show that coupling of TGF-β signaling and ECM assembly is essential for proper development and is achieved in multiple human organ systems by multifunctional proteins such as LTBP4.
