UMR 1231 GAD, Génétique des Anomalies du Développement, Université de Bourgogne- et Franche-Comté, Dijon, France.
FHU TRANSLAD, Centre Hospitalier Universitaire de Bourgogne et Franche Comté, Dijon, France.
Clin Genet. 2018 Jun;93(6):1205-1209. doi: 10.1111/cge.13238. Epub 2018 Apr 6.
Oral-facial-digital (OFD) syndromes are a subgroup of ciliopathies distinguished by the co-occurrence of hamartomas and/or multiple frenula of the oral region and digital anomalies. Several clinical forms of OFD syndromes are distinguished by their associated anomalies and/or inheritance patterns, and at least 20 genetic types of OFD syndromes have been delineated. We describe here a child with preaxial and postaxial polydactyly, lingual hamartoma, a congenital heart defect, delayed development and cerebellar peduncles displaying the molar tooth sign. Whole-exome sequencing and SNP array identified compound heterozygous variants in the INTU gene, which encodes a protein involved in the positioning of the ciliary basal body. INTU is a subunit of the CPLANE multiprotein complex essential for the assembly of IFT-A particles and intraflagellar transport. This report of a second patient with INTU-related OFD syndrome and the further delineation of its neuroimaging and skeletal phenotype now allow INTU-related OFD syndromes to be classified within the OFD syndrome type VI group. Patients display a phenotype similar to that of mice with a hypomorphic mutation of Intu, but with the addition of a heart defect.
口腔面指（OFD）综合征是纤毛病的一个亚组，其特征是口腔区域的错构瘤和/或多个系带与数字异常同时发生。OFD 综合征有几种临床形式，其特征是相关的异常和/或遗传模式，并且已经确定了至少 20 种 OFD 综合征的遗传类型。我们在此描述了一名患有前轴和后轴多指、舌部错构瘤、先天性心脏缺陷、发育迟缓以及小脑脚呈磨牙征的患儿。全外显子组测序和 SNP 芯片鉴定了 INTU 基因的复合杂合变异，该基因编码一种参与纤毛基底体定位的蛋白。INTU 是 CPLANE 多蛋白复合物的一个亚基，对于 IFT-A 颗粒的组装和鞭毛内运输至关重要。这是第二位与 INTU 相关的 OFD 综合征患者的报告，并进一步阐明了其神经影像学和骨骼表型，现在可以将 INTU 相关的 OFD 综合征分类为 OFD 综合征 VI 型。患者表现出与 Intu 功能减弱突变的小鼠相似的表型，但伴有心脏缺陷。
