Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III
Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III
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DOI：
10.1086/316926
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发表时间：
2001-01-01
影响因子：
9.8
通讯作者：
Horsthemke, B
中科院分区：
文献类型：
--
作者：
Lüdecke, HJ;Schaper, J;Horsthemke, B
Tricho-rhino-phalangeal综合征（TRPS）以颅面和骨骼异常为特征。已经描述了三种亚型：TRPS I，由8号染色体上TRPS1基因突变引起；TRPS II，一种影响TRPS1和EXT1基因的微缺失综合征；TRPS III型，由于掌骨短，严重短促，身材严重矮小，但没有外植骨。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患者短指的高度和程度。我们在51名无关患者中的44名患者中发现了35种不同的突变。检出率（86%）表明TRPS1是TRPS I和TRPS III的主要位点。我们未在散发性患者的父母或家族性患者的明显健康亲属中发现任何突变，表明TRPS1突变完全外显。对TRPS1突变患者骨骼异常的评估揭示了广泛的临床谱。在不相关的、年龄和性别匹配的具有相同突变的患者中，以及在家庭中，表型是可变的。5个错义突变中有4个改变了GATA dna结合锌指，7个不相关的突变患者中有6个可能被归类为TRPS III。我们的数据表明，TRPS III处于TRPS谱系的严重端，并且最常由TRPS1基因的特定类型突变引起。
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 brachydaayly, 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.