Lüdecke H J, Schaper J, Meinecke P, Momeni P, Gross S, Hirche H, Abramowicz M J, Albrecht B, Apacik C, Christen H J, Claussen U, Devriendt K, Fastnacht E, Forderer A, Friedrich U, Goodship T H, Greiwe M, Hamm H, Hennekam R C, Hinkel G K, Hoeltzenbein M, Kayserili H, Majewski F, Mathieu M, McLeod R, Midro A T, Moog U, Nagai T, Niikawa N, Orstavik K H, Plöchl E, Seitz C, Schmidtke J, Tranebjaerg L, Tsukahara M, Wittwer B, Zabel B, Gillessen-Kaesbach G, Horsthemke B
Institut für Humangenetik, Universitätsklinikum, 45122 Essen, Germany.
Am J Hum Genet. 2001 Jan;68(1):81-91. doi: 10.1086/316926. Epub 2000 Dec 7.
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.
毛发-鼻-指综合征（TRPS）的特征为颅面和骨骼异常。已描述了三种亚型：TRPS I，由8号染色体上TRPS1基因的突变引起；TRPS II，一种影响TRPS1和EXT1基因的微缺失综合征；以及TRPS III，一种因掌骨短而导致严重短指畸形和严重身材矮小，但无外生骨疣的类型。为了研究TRPS III是否由TRPS1突变引起，并建立TRPS的基因型-表型相关性，我们进行了广泛的突变分析，并评估了TRPS I或TRPS III患者的身高和短指畸形程度。我们在51例无关患者中的44例中发现了35种不同的突变。检出率（86%）表明TRPS1是TRPS I和TRPS III的主要基因座。我们在散发患者的父母或家族性患者的明显健康亲属中未发现任何突变，表明TRPS1突变具有完全外显率。对TRPS1突变患者的骨骼异常评估显示出广泛的临床谱。在具有相同突变的无关、年龄和性别匹配的患者以及家族中，表型是可变的。五个错义突变中的四个改变了GATA DNA结合锌指，七名具有这些突变的无关患者中有六名可归类为患有TRPS III。我们的数据表明，TRPS III处于TRPS谱的严重一端，并且它最常由TRPS1基因中的一类特定突变引起。
