Al-Bakheet Albandary, Tohary Mohamed, Khan Sameena, Chedrawi Aziza, Edrees Alaa, Tous Ehab, Al-Mousa Hamoud, Al-Otaibi Lefian, AlShahrani Saif, Alsagob Maysoon, Al-Quait Laila, Almass Rawan, Al-Joudi Haya, Monies Dorota, Al-Semari Abdulaziz, Aldosary Mazhor, Daghestani Maha, Colak Dilek, Kaya Namik, Al-Owain Mohammed
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Clin Genet. 2021 May;99(5):724-731. doi: 10.1111/cge.13932. Epub 2021 Mar 5.
The dysfunction of microtubules (α/β-tubulin polymers) underlies a wide range of nervous system genetic abnormalities. Defects in TBCD, a tubulin-folding cofactor, cause diseases highlighted with early-onset encephalopathy with or without neurodegeneration, intellectual disability, seizures, microcephaly and tetraparaperesis. Utilizing various molecular methods, we describe nine patients from four unrelated families with two novel exon 18 variants in TBCD exhibiting the typical neurological phenotype of the disease. Interestingly, all the investigated patients had previously unreported hematological findings in the form of neutropenia and mild degree of anemia and thrombocytopenia. In addition to delineating the neurological phenotype in several patients with TBCD variants, our study stresses on the new association of neutropenia, in particular, with the disease.
微管（α/β-微管蛋白聚合物）功能障碍是多种神经系统遗传异常的基础。微管蛋白折叠辅助因子TBCD的缺陷会引发一些疾病，其特征为早发性脑病，伴有或不伴有神经退行性变、智力残疾、癫痫、小头畸形和四肢轻瘫。我们运用多种分子方法，描述了来自四个无亲缘关系家庭的九名患者，他们的TBCD基因外显子18存在两种新的变异，表现出该疾病典型的神经学表型。有趣的是，所有接受调查的患者此前都有未报告的血液学表现，即中性粒细胞减少以及轻度贫血和血小板减少。除了描绘出几名携带TBCD变异患者的神经学表型外，我们的研究还强调了中性粒细胞减少，特别是与该疾病的新关联。
