Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy.
CEINGE Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy.
Genes (Basel). 2024 Sep 9;15(9):1184. doi: 10.3390/genes15091184.
The gene encodes a component of the cohesin complex, involved in chromosome segregation and DNA repair. Variants in genes of the cohesin complex determine clinical conditions characterized by facial dysmorphisms, upper limb anomalies, intellectual disability, and other neurological deficits. However, to date, the -related clinical phenotype has been poorly investigated (around 20 cases reported).
We report, for the first time, two twins affected by a syndromic neurodevelopmental disorder associated with a de novo variant in the gene. Although both the twins showed a neurodevelopmental delay, one of them showed a more severe phenotype with greater behavioral problems, speech defects and limb apraxia. CGH array showed a 15q13.3 microduplication, inherited from an unaffected mother.
We found different degrees of behavioral, speech and cognitive impairment in two twins affected by a neurodevelopmental disorder associated with a variant. These findings highlight the variability of the -associated phenotype or a probable role of associated variants (like the discovered 15q13.3 microduplication) in modulating the clinical features.
该基因编码着黏合蛋白复合体的一个组成部分，参与染色体分离和 DNA 修复。黏合蛋白复合体基因的变异可导致具有面部畸形、上肢异常、智力障碍和其他神经缺陷等临床特征的病症。然而，迄今为止，与该基因相关的临床表型研究甚少（约有 20 例报道）。
我们首次报道了一对受神经发育障碍综合征影响的双胞胎，其发病与基因中的新生变异有关。尽管两个双胞胎均表现出神经发育迟缓，但其中一个表现出更为严重的表型，具有更多的行为问题、言语缺陷和肢体运动障碍。CGH 微阵列分析显示，该双胞胎之一从未受影响的母亲那里遗传了 15q13.3 微重复。
我们发现，一对受神经发育障碍影响的双胞胎存在不同程度的行为、言语和认知障碍，其与基因变异有关。这些发现突出了与基因相关的表型的变异性，或相关变异（如发现的 15q13.3 微重复）在调节临床特征方面的可能作用。
