Brancati Francesco, Barrano Giuseppe, Silhavy Jennifer L, Marsh Sarah E, Travaglini Lorena, Bielas Stephanie L, Amorini Maria, Zablocka Dominika, Kayserili Hulya, Al-Gazali Lihadh, Bertini Enrico, Boltshauser Eugen, D'Hooghe Marc, Fazzi Elisa, Fenerci Elif Y, Hennekam Raoul C M, Kiss Andrea, Lees Melissa M, Marco Elysa, Phadke Shubha R, Rigoli Luciana, Romano Stephane, Salpietro Carmelo D, Sherr Elliott H, Signorini Sabrina, Stromme Petter, Stuart Bernard, Sztriha Laszlo, Viskochil David H, Yuksel Adnan, Dallapiccola Bruno, Valente Enza Maria, Gleeson Joseph G
IRCCS CSS, Mendel Institute, viale Regina Margherita 261, 00198, Rome, Italy.
Am J Hum Genet. 2007 Jul;81(1):104-13. doi: 10.1086/519026. Epub 2007 May 18.
Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MTS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Loken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.
乔伯特综合征相关疾病（JSRDs）是一组临床和遗传异质性疾病，它们都存在中脑-后脑畸形，即脑部影像学上可见的磨牙征（MTS），伴有不同的神经、眼部和肾脏表现。最近在具有MTS相关神经特征的家族中发现了CEP290基因突变，其中许多家族表现出典型的Senior-Loken综合征眼肾受累（JSRD-SLS表型）。在此，我们对两个不重叠的经证实有MTS的JSRD患者队列进行了全面的CEP290基因突变分析。我们在44例JSRD-SLS患者中的19例中发现了突变。第二个队列由84例代表其他JSRD亚型的患者组成，仅在2例患者中发现了突变。数据表明，CEP290基因突变很常见，且在很大程度上是JSRD-SLS亚型所特有的。一名有突变的患者表现为完全内脏反位，证实了JSRDs与其他纤毛病之间的临床和遗传重叠。
