Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
Department of Imaging Diagnosis, Universidade Federal de São Paulo, São Paulo, Brazil.
Cytogenet Genome Res. 2022;162(1-2):46-54. doi: 10.1159/000522034. Epub 2022 Mar 15.
Langer-Giedion syndrome (LGS) is caused by a contiguous deletion at 8q23q24, characterized by exostoses, facial, ectodermal, and skeletal anomalies, and, occasionally, intellectual disability. LGS patients have been diagnosed clinically or by routine cytogenetic techniques, hampering the definition of an accurate genotype-phenotype correlation for the syndrome. We report two unrelated patients with 8q23q24 deletions, characterized by cytogenomic techniques, with one of them, to our knowledge, carrying the smallest deletion reported in classic LGS cases. We assessed the pathogenicity of the deletion of genes within the 8q23q24 region and reviewed other molecularly confirmed cases from the literature. Our findings suggest a 3.2-Mb critical region for a typical presentation of the syndrome, emphasizing the contribution of the TRPS1, RAD21, and EXT1 genes' haploinsufficiency, and facial dysmorphisms as well as bone anomalies as the most frequent features among patients with LGS. We also suggest a possible role for the CSMD3 gene, whose deletion seems to contribute to central nervous system anomalies. Since studies performing such correlation for LGS patients are limited, our data contribute to improving the ge-notype-phenotype characterization for LGS patients.
朗格-吉伊登综合征（LGS）由 8q23q24 连续缺失引起，其特征为外生骨疣、面部、外胚层和骨骼异常，偶尔伴有智力障碍。LGS 患者通过临床或常规细胞遗传学技术进行诊断，这妨碍了对该综合征进行准确的基因型-表型相关性定义。我们报告了两例无关的 8q23q24 缺失患者，采用细胞遗传学技术进行了特征描述，据我们所知，其中一例患者携带经典 LGS 病例中报道的最小缺失。我们评估了 8q23q24 区域内基因缺失的致病性，并回顾了文献中其他分子证实的病例。我们的发现提示存在一个 3.2Mb 的关键区域，对于典型的综合征表现具有重要意义，强调了 TRPS1、RAD21 和 EXT1 基因单倍不足、面部畸形以及骨骼异常作为 LGS 患者最常见的特征。我们还提出了 CSMD3 基因的可能作用，其缺失似乎与中枢神经系统异常有关。由于对 LGS 患者进行这种相关性研究有限，我们的数据有助于改善 LGS 患者的基因型-表型特征。
